Neuroendocrine-Immune Regulatory Network of Eucommia ulmoides Oliver.

Eucommia ulmoides Oliver (E. ulmoides) is a popular medicinal herb and health supplement in China, Japan, and Korea, and has a variety of pharmaceutical properties. The neuroendocrine-immune (NEI) network is crucial in maintaining homeostasis and physical or psychological functions at a holistic level, consistent with the regulatory theory of natural medicine. This review aims to systematically summarize the chemical compositions, biological roles, and pharmacological properties of E. ulmoides to build a bridge between it and NEI-associated diseases and to provide a perspective for the development of its new clinical applications. After a review of the literature, we found that E. ulmoides has effects on NEI-related diseases including cancer, neurodegenerative disease, hyperlipidemia, osteoporosis, insomnia, hypertension, diabetes mellitus, and obesity. However, clinical studies on E. ulmoides were scarce. In addition, E. ulmoides derivatives are diverse in China, and they are mainly used to enhance immunity, improve hepatic damage, strengthen bones, and lower blood pressure. Through network pharmacological analysis, we uncovered the possibility that E. ulmoides is involved in functional interactions with cancer development, insulin resistance, NAFLD, and various inflammatory pathways associated with NEI diseases. Overall, this review suggests that E. ulmoides has a wide range of applications for NEI-related diseases and provides a direction for its future research and development.

In vitro fecal fermentation properties of polysaccharides from Tremella fuciformis and related modulation effects on gut microbiota.

Tremella fuciformis is an edible and medicinal mushroom. Polysaccharides from T. fuciformis have received increasing attention due to their diversely pharmacological activities. In this study, the digestive behavior and fermentation characteristics of T. fuciformis polysaccharides (TFP) were studied. The results revealed that the reducing sugar content, chemical composition, molecular weight, rheological property, constituent monosaccharide, and FT-IR spectrum of TFP were not altered after the in vitro simulated digestion, indicating that it was indigestible under different simulated digestion conditions. However, the physicochemical characteristics of TFP, including reducing sugar content, molecular weight, constituent monosaccharide, and free monosaccharide released, were obviously altered after the in vitro fermentation for 48 h, indicating that it was remarkably utilized by intestinal microbiota in human feces. Notably, TFP could obviously modulate the microbial composition via promoting the relative abundances of Phascolarctobacterium, Bacteroides, and Lachnoclostridium. Moreover, TFP could also increase the production of short-chain fatty acids, including acetic, propionic, n-butyric, and n-valeric acids, after the in vitro fermentation for 48 h. These results showed that TFP was stable under the simulated digestion conditions, but could be utilized by intestinal microbiota in human feces, and might possess the potential to improve intestinal health.

In vitro digestive characteristics and microbial degradation of polysaccharides from lotus leaves and related effects on the modulation of intestinal microbiota.

Polysaccharides exist as one of the most abundant components in lotus leaves, which attract increasing attention owing to their promising health-promoting benefits. In this study, the digestive and microbial degradation characteristics of lotus leaf polysaccharides (LLP) were studied by using an in vitro gastrointestinal model. The results suggested that LLP was stable in the human upper gastrointestinal tract in vitro according to its digestive stabilities at different simulated digestion stages. Conversely, the indigestible LLP (LLPI) could be remarkably utilized by intestinal microbiota in human feces during in vitro fermentation, and its fermentability was 58.11% after the in vitro fermentation of 48 h. Indeed, the microbial degradation characteristics of LLPI during in vitro fermentation by human fecal inoculum were revealed. The results showed that the content of reducing sugars released from LLPI obviously increased from 0.498 to 2.176 mg/mL at the initial fermentation stage (0-6 h), and its molecular weight sharply decreased from 4.08 × 104 to 2.02 × 104 Da. Notably, the molar ratios of arabinose (Ara), galactose (Gal), and galacturonic acid (GalA) in LLPI decreased from 2.89 to 1.40, from 5.46 to 3.72, and from 21.24 to 18.71, respectively, suggesting that the utilization of arabinose and galactose in LLPI by intestinal microbiota was much faster than that of galacturonic acid at the initial fermentation stage. Additionally, LLPI could remarkably regulate gut microbial composition by increasing the abundances of several beneficial microbes, including Bacteroides, Bifidobacterium, Megamonas, and Collinsella, resulting in the promoted generation of several short-chain fatty acids, especially acetic, propionic, and butyric acids. The findings from the present study are beneficial to better understanding the digestive and microbial degradation characteristics of LLP, which indicate that LLP can be used as a potential prebiotic for the improvement of intestinal health.

Hydroxysafflor Yellow A Blocks HIF-1α Induction of NOX2 and Protects ZO-1 Protein in Cerebral Microvascular Endothelium.

Zonula occludens-1 (ZO-1) is a tight junction protein in the cerebrovascular endothelium, responsible for blood-brain barrier function. Hydroxysafflor yellow A (HSYA) is a major ingredient of safflower (Carthamus tinctorius L.) with antioxidative activity. This study investigated whether HSYA protected ZO-1 by targeting ROS-generating NADPH oxidases (NOXs). HSYA administration reduced cerebral vascular leakage with ZO-1 protection in mice after photothrombotic stroke, largely due to suppression of ROS-associated inflammation. In LPS-stimulated brain microvascular endothelial cells, HSYA increased the ratio of NAD+/NADH to restore Sirt1 induction, which bound to Von Hippel-Lindau to promote HIF-1αdegradation. NOX2 was the predominant isoform of NOXs in endothelial cells and HIF-1α transcriptionally upregulated p47phox and Nox2 subunits for the assembly of the NOX2 complex, but the signaling cascades were blocked by HSYA via HIF-1α inactivation. When oxidate stress impaired ZO-1 protein, HSYA attenuated carbonyl modification and prevented ZO-1 protein from 20S proteasomal degradation, eventually protecting endothelial integrity. In microvascular ZO-1 deficient mice, we further confirmed that HSYA protected cerebrovascular integrity and attenuated ischemic injury in a manner that was dependent on ZO-1 protection. HSYA blocked HIF-1α/NOX2 signaling cascades to protect ZO-1 stability, suggestive of a potential therapeutic strategy against ischemic brain injury.

Dynamic variations in physicochemical characteristics of oolong tea polysaccharides during simulated digestion and fecal fermentation in vitro.

In this study, dynamic variations in physicochemical characteristics of polysaccharides from 'Wuyi rock' tea (WYP) at different simulated digestion and fecal fermentation stages in vitro were studied. Results revealed that physicochemical characteristics of WYP were slightly altered after the simulated digestion in vitro, and its digestibility was about 8.38%. Conversely, physicochemical characteristics of the indigestible WYP, including reducing sugar, chemical composition, constituent monosaccharide, molecular weight, and FT-IR spectrum, were obviously altered after the fecal fermentation in vitro, and its fermentability was about 42.18%. Notably, the indigestible WYP could remarkably modulate the microbial composition via promoting the proliferation of profitable intestinal microbes, such as Bacteroides, Lactococcus, and Bifidobacterium. Moreover, it could also enhance the generation of short-chain fatty acids. The results showed that WYP was slightly digested in the gastrointestinal tract in vitro, but could be obviously utilized by intestinal microbiota, and might possess the potential to improve intestinal health.

GDF11 knockdown downregulates SMURF1 to inhibit breast cancer progression by activation of p53 and inactivation of ERα signaling.

Breast cancer (BC) is a prevalent neoplasm that occurs in women all over the world. Growth and differentiation factor 11 (GDF11) plays an essential role in cancer progression. This study focused on investigating the biological role and underlying mechanisms of GDF11 in BC. We detected the expression of GDF11 in 27 patients with BC and BC cell lines. Kaplan-Meier plotter was employed to analyze the relationship between GDF11 expression and overall survival (OS) of BC patients. The proliferative, migratory, invasive, and apoptotic abilities of T47D cells were examined. Correlation analysis of GDF11 with Smad ubiquitination regulatory factor 1 (SMURF1) was conducted. The association between GDF11 and the p53 pathway was analyzed by western blot and PFT-α (a p53 inhibitor)-mediated rescue assays. A brief analysis of the role of estrogen receptor alpha (ERα) signaling in BC progression was performed. The results showed that GDF11 was increased in BC tissues and cell lines, and the high expression of GDF11 was associated with the poor OS of BC patients. GDF11 knockdown inhibited the proliferation, migration, and invasion of T47D cells, but promoted cell apoptosis. Meanwhile, the GDF11 knockdown reduced the SMURF1 expression and invoked the p53 pathway activation. SMURF1 overexpression and PFT-α partially blocked the effects of GDF11 knockdown. In addition, GDF11 knockdown and SMURF1 silencing inhibited the activation of the ERα signaling pathway. In summary, GDF11 was involved in the progression of BC by regulating SMURF1-mediated p53 and ERα pathways, opening up a new way for BC treatment.

HIF-1: structure, biology and natural modulators.

Hypoxia-inducible factor 1 (HIF-1), as a main transcriptional regulator of metabolic adaptation to changes in the oxygen environment, participates in many physiological and pathological processes in the body, and is closely related to the pathogenesis of many diseases. This review outlines the mechanisms of HIF-1 activation, its signaling pathways, natural inhibitors, and its roles in diseases. This article can provide new insights in the diagnosis and treatment of human diseases, and recent progress on the development of HIF-1 inhibitors.

Dynamic changes of structural characteristics of snow chrysanthemum polysaccharides during in vitro digestion and fecal fermentation and related impacts on gut microbiota.

The in vitro simulated saliva-gastrointestinal digestion and human fecal fermentation of snow chrysanthemum polysaccharides (JHP) were investigated. Results showed that reducing sugar contents of JHP increased during the gastrointestinal digestion, and glucose released with the decrease of its molecular weight, suggesting that JHP could be partially degraded under the gastrointestinal digestion. Furthermore, after in vitro fecal fermentation, the molecular weight and molar ratio of constituent monosaccharides (galactose and galacturonic acid) of the indigestible JHP (JHP-I) significantly decreased, and both monosaccharides and oligosaccharides released, suggesting that JHP-I could be further degraded and consumed by gut microbiota. Some beneficial bacteria, such as genera Bifidobacterium, Lactobacillus, Megamonas, and Megasphaera, significantly increased, suggesting that JHP-I could change the composition and abundance of gut microbiota. These results suggest that JHP is a potential source of prebiotics, and can be helpful for better understanding of the potential digestion and fermentation mechanism of JHP.

Regulation of the NLRP3 inflammasome with natural products against chemical-induced liver injury.

The past decades have witnessed significant progress in understanding the process of sterile inflammation, which is dependent on a cytosolic complex termed the nucleotide-binding oligomerization domain (NOD)-like receptor containing pyrin domain 3 (NLRP3) inflammasome. Activation of NLRP3 inflammasome requires two steps, including the activation of Toll-like receptor (TLR) by its ligands, resulting in transcriptional procytokine and inflammasome component activation, and the assembly and activation of NLRP3 inflammasome triggered by various danger signals, leading to caspase-1 activation, which could subsequently cleave procytokines into their active forms. Metabolic disorders, ischemia and reperfusion, viral infection and chemical insults are common pathogenic factors of liver-related diseases that usually cause tissue damage and cell death, providing numerous danger signals for the activation of NLRP3 inflammasome. Currently, natural products have attracted much attention as potential agents for the prevention and treatment of liver diseases due to their multitargets and nontoxic natures. A great number of natural products have been shown to exhibit beneficial effects on liver injury induced by various chemicals through regulating NLRP3 inflammasome pathways. In this review, the roles of the NLRP3 inflammasome in chemical-induced liver injury (CILI) and natural products that exhibit beneficial effects in CILI through the regulation of inflammasomes were systematically summarized.

In vitro simulated digestion and fecal fermentation of polysaccharides from loquat leaves: Dynamic changes in physicochemical properties and impacts on human gut microbiota.

The aim of this study was to well understand the dynamic changes of physicochemical properties of polysaccharides from loquat leaves (LLP) during in vitro simulated saliva-gastrointestinal digestion and fecal fermentation and its related impacts on human gut microbiota. Results showed that the contents of reducing sugar of LLP slightly increased during the gastrointestinal digestion, and its molecular weight also slightly decreased, suggesting that LLP could be slightly degraded under the gastrointestinal digestion conditions. Moreover, during the fecal fermentation, the molecular weight of the indigestible LLP (LLP-I) significantly decreased, and the molar ratio of constituent monosaccharides of LLP-I, such as glucuronic acid, galacturonic acid, galactose, and arabinose, significantly changed, indicating that LLP-I could be degraded and consumed by human gut microbiota. Indeed, some beneficial bacteria such as Megasphaera, Megamonas, Bifidobacterium, Phascolarctobacterium, and Desulfovibrio significantly increased, suggesting that LLP-I could change the composition and abundance of gut microbiota. LLP-I could also promote the production of health-promoting short chain fatty acids. Results from this study are benefical to well understand the in vitro digestion and fecal fermentation behaviors of LLP, and LLP can be developed as a potential prebiotic in the functional food industry.

Polysaccharides from dandelion (Taraxacum mongolicum) leaves: Insights into innovative drying techniques on their structural characteristics and biological activities.

The aim of this study was to well understand the impacts of innovative drying techniques (radio frequency drying and microwave drying) and traditional drying techniques (vacuum drying, freezing drying, and hot air drying) on the structural characteristics and bioactivities of polysaccharides from dandelion leaves (DLPs). Five different DLPs were obtained from dandelion leaves dried by abovementioned drying techniques. Results showed that the structural characteristics and bioactivities of DLPs varied with different drying techniques. The molecular weights, apparent viscosities, molar ratios of constituent monosaccharide, contents of uronic acids, and contents of bonded polyphenolics in DLPs obtained by different drying techniques had noticeable variations, while the types of constituent monosaccharides and the major glycosidic linkages in DLPs were similar. In addition, results showed that DLPs, especially DLP-RF obtained by the radio frequency drying, exhibited remarkable antioxidant activities (ABTS, DPPH, and NO radical scavenging activities), excellent in vitro antiglycation activity, and obvious in vitro inhibitory activity on α-glucosidase. Results from this study suggest that the radio frequency drying can be used as a potential drying technique before extracting DLPs for applications in the functional food and medicine industries.

Effects of simulated saliva-gastrointestinal digestion on the physicochemical properties and bioactivities of okra polysaccharides.

This study was to investigate the effects of in vitro simulated saliva-gastrointestinal digestion on the physicochemical properties and bioactivities of okra polysaccharides (OPS). Results showed that the digestibilities of OPS were about 5.1%, 37.5%, and 41.3% after saliva digestion (SD), saliva-gastric digestion (SGD), and saliva-gastrointestinal digestion (SGID), respectively. The SGID significantly changed the physicochemical properties of OPS, such as total uronic acids, total flavonoids, monosaccharide composition, rheological properties, and molecular weights (Mw). Especially, Mw changes resulted in the breakdown of glycosidic bonds during SGD, and the degradation of OPS during SGID was mainly caused by disrupting aggregates. Furthermore, the bioactivities of OPS were also affected by SGID. After SGID, OPS still possessed strong antioxidant activities, binding capacities, and prebiotic activities, but the α-glucosidase inhibitory effect was obviously decreased. Overall, results can provide valuable and scientific support on the oral administration of OPS as functional foods and medicines in the future.

Quantitative Characterization of Ginsenoside Biotransformation in Panax notoginseng Inflorescences and Leaves by Online Two-Dimensional Liquid Chromatography Coupled to Mass Spectrometry.

Panax notoginseng inflorescences (PNI) and leaves (PNL) are commonly used as folk medicine and food supplements. In this study, an online two-dimensional hydrophilic interaction × reversed-phase liquid chromatography coupled to linear trap quadropole mass spectrometry method was developed to determine 24 ginsenosides, including two novel compounds, in PNI and PNL extracted by water and methanol. Our data demonstrated that ginsenosides Rd, Rc, Rb2, Rb3, Rb1, Ra2, Ra1, and Ra3 in both PNI and PNL extracted by water rather than methanol can be transformed to ginsenoside F2, notoginsenoside Fe, ginsenoside Rd2, notoginsenoside Fd, gypenoside XVII, PN02, PN01, and PN03, respectively, by selectively cleaving the ß-(1→2)-glucosidic linkage at the C-3 position. Ginsenoside transformation was further verified to be mediated by the proteins isolated from samples. Additionally, the two newly discovered transformed products, namely, PN02 and PN03, were prepared and identified as novel compounds by nuclear magnetic resonance. Our findings provide new insight into the importance of extraction solvents on the component profile of natural products.

Structural characterization, antioxidant activity, and immunomodulatory activity of non-starch polysaccharides from Chuanminshen violaceum collected from different regions.

Chuanminshen violaceum has been used as an important traditional Chinese medicine and a popular tonic food in China. Polysaccharides are considered the major bioactive components in C. violaceum. In this study, in order well understand the chemical structures and bioactivities of non-starch polysaccharides in C. violaceum (CVPs), the physicochemical structures, antioxidant activities, and immunomodulatory activities of CVPs in C. violaceum collected from different regions of China were investigated and compared. Results showed that the constituent monosaccharides and Fourier transform infrared spectra of CVPs in C. violaceum collected from different regions were similar. However, their molar ratios of constituent monosaccharides, molecular weights, and contents of uronic acids were different. Furthermore, CVPs exerted remarkable antioxidant activities (ABTS and nitric oxide radical scavenging capacities) and immunomodulatory activities (promoted production of nitric oxide, IL-6, and TNF-α from RAW 264.7 macrophages in vitro). Meanwhile, the antioxidant and immunomodulatory activities of CVPs extracted from C. violaceum also varied by cultivated regions. Moreover, results indicated that the antioxidant and immunomodulatory activities of CVPs were closely correlated to their α-1,4-d-galactosiduronic linkages. Results are helpful for better understanding of the structure-bioactivity relationships of CVPs, and beneficial for the improvement of their applications in pharmaceutical and functional food industries.

Comprehensively qualitative and quantitative analysis of ginsenosides in Panax notoginseng leaves by online two-dimensional liquid chromatography coupled to hybrid linear ion trap Orbitrap mass spectrometry with deeply optimized dilution and modulation system.

Panax notoginseng leaves (PNL) was considered as a potential medicinal part with abundant protopanaxdiol type ginsenosides. In this study, an integrated system was developed for simultaneously qualitative and quantitative analysis of ginsenosides in PNL using online comprehensive two-dimensional hydrophilic interaction chromatography and reversed-phase liquid chromatography coupled to a hybrid linear ion trap-Orbitrap mass spectrometry (online HILIC × RP-ESI/HRMS/MSn). The system was configured based on the combination of a XBridge amide column (150 mm × 2.1 mm, 2.5 µm) and Accucore phenyl-hexyl (50 mm × 4.6 mm, 2.6 µm) for the first and second dimensions, respectively. An additional water phase was introduced to dilute the eluent from the first dimension to decrease its elution strength in the second dimension. The online dilution, modulation interface and the second-dimension gradient program were deeply optimized to reduce possible sample loss and improve system resolution. Under the optimal conditions, a total of 226 ginsenosides were unambiguously identified or tentatively characterized by aid of high-resolution accurate mass and MSn fragment data in both negative and positive ion modes, and 93 of them were discovered as potentially new ginsenosides in PNL. Besides, the validated online HILIC × RP-LTQ-MS method was applied to determine 24 ginsenosides directly on 2D-EIC contour plots in nine batches of PNL samples. The powerful separation capability acquired by the developed online HILIC × RP system affords not only reliable structural information for identification, but also accurate quantitation. This combined system can also be used to characterize and quantify bioactive ingredients in the samples with complex matrices.

Modulation of electroosmotic flow in capillary electrophoresis by plant polyphenol-inspired gallic acid/polyethyleneimine coatings: Analysis of small molecules.

Plant polyphenols can form functional coatings on various materials through self-polymerization. In this paper, a series of modified capillary columns, which possess diversity of charge characteristics for modulating electroosmotic flow (EOF), were prepared by one-step co-deposition of gallic acid (GA), a plant-derived polyphenol monomer, and branched polyethyleneimine (PEI). The physicochemical properties of the prepared columns were characterized by Fourier transform infrared spectroscopy (FT-IR), UV-Vis spectroscopy and scanning electron microscopy (SEM). The magnitude and direction of EOF of GA/PEI co-deposited columns were modulated by changing a series of coating parameters, such as post-incubation of FeCl3, co-deposition time, and deposited amounts of GA and PEI with different relative molecular mass (PEI-600, PEI-1800, PEI-10000, and PEI-70000). Furthermore, the separation efficiencies of the prepared GA/PEI co-deposited columns were evaluated by separations of small molecules, including organic acids, polar nucleotides, phenols, nucleic acid bases and nucleosides. Results indicated that modulating of EOF plays an important role in enhancing the separation performance and reversing the elution order of the analytes. Finally, the developed method was successfully applied to quantitative analysis of acidic compounds in four real samples. The recoveries were in the range of 73.5%-85.8% for citric acid, benzoic acid, sorbic acid, salicylic acid and ascorbic acid in beverage and fruit samples, 101.6%-104.9% for cinnamic acid, vanillic acid, and ferulic acid in Angelica sinensis sample, while 84.6%-97.8% for guanosine-5'-monophosphate, uridine-5'-monophosphate, cytosine-5'- monophosphate and adenosine-5'-monophosphate in Cordyceps samples. These results indicated that the co-deposition of plant polyphenol-inspired GA/PEI coatings can provide new opportunities for EOF modulation of capillary electrophoresis.

Cupric ion functionalized polydopamine coated magnetic microspheres as solid-phase adsorbent for the extraction of purines in plasma.

In this paper, Cu2+ functionalized Fe3O4@polydopamine core-shell (Fe3O4@PDA@Cu2+) magnetic microspheres were prepared by the chelation between Cu2+ and catechol of polydopamine surface. The synthetic magnetic adsorbent was characterized by Fourier transform infrared spectroscopy, energy dispersive X-ray spectroscopy, vibrating sample magnetometry, thermogravimetric analysis, scanning electron microscope and transmission electron microscopy. Four purines include guanine, adenine, hypoxanthine and xanthine were selected as model compounds to evaluate the applicability of this adsorbent. Several parameters that effected the extraction efficiency, such as extraction time, adsorbent amount, solution pH, ionic strength, eluent type, concentration of eluent and eluent time, were investigated. Under the optimized conditions, good linearity was obtained with correlation coefficients between 0.9983 and 0.9999 for the four analytes, and their LOD and LOQ were 0.42-2.15 ng/mL and 1.41-6.50 ng/mL, respectively. Meanwhile, the RSDs of intra-day and inter-day precision were in the range of 1.43%-5.55% and 4.56%-7.01%, respectively. The spiked recoveries of four purines in real sample were 70.01%-102.42%, indicating this proposed method might have potential applications for the analysis of purines in real samples. In addition, the developed method was used to monitor the concentrations of adenine in rat plasma at different time points after intragastric administration.

Structural characterization, antioxidant activity, and antiglycation activity of polysaccharides from different chrysanthemum teas.

Polysaccharides are one of the major bioactive components in chrysanthemum teas. In order to understand well the chemical structures and bioactivities of polysaccharides from different chrysanthemum teas (JHPs) collected in China, the physicochemical characteristics, antioxidant activity, and antiglycation activity of polysaccharides extracted from different chrysanthemum teas, including Coreopsis tinctoria, Chrysanthemum indicum, C. morifolium 'Huangju', C. morifolium 'Gongju', and C. morifolium 'Hangbaiju', were investigated. The results showed that the contents of total uronic acids and total phenolics in JHPs ranged from (28.4 ± 0.3)% to (36.2 ± 0.2)%, and from 9.4 ± 0.7 to 70.2 ± 1.7 mg GAE per g, respectively. The molecular weights of fraction 1 and fraction 2 in JHPs ranged from 4.29 × 105 to 5.88 × 105 Da, and from 4.11 × 104 to 5.24 × 104 Da, respectively. The dominant constituent monosaccharides of JHPs were galacturonic acid, arabinose, and galactose. Furthermore, JHPs, especially polysaccharides extracted from C. tinctoria, exerted remarkable ABTS, DPPH, nitric oxide, and hydroxyl radical scavenging activities, as well as strong antiglycation activities. The results are helpful for better understanding of the chemical structures and bioactivities of JHPs, and JHPs may have good potential applications in the functional-food industry.

Furanodiene Induces Extrinsic and Intrinsic Apoptosis in Doxorubicin-Resistant MCF-7 Breast Cancer Cells via NF-κB-Independent Mechanism.

Chemotherapy is used as a primary approach in cancer treatment after routine surgery. However, chemo-resistance tends to occur when chemotherapy is used clinically, resulting in poor prognosis and recurrence. Currently, Chinese medicine may provide insight into the design of new therapies to overcome chemo-resistance. Furanodiene, as a heat-sensitive sesquiterpene, is isolated from the essential oil of Rhizoma Curcumae. Even though mounting evidence claiming that furanodiene possesses anti-cancer activities in various types of cancers, the underlying mechanisms against chemo-resistant cancer are not fully clear. Our study found that furanodiene could display anti-cancer effects by inhibiting cell viability, inducing cell cytotoxicity, and suppressing cell proliferation in doxorubicin-resistant MCF-7 breast cancer cells. Furthermore, furanodiene preferentially causes apoptosis by interfering with intrinsic/extrinsic-dependent and NF-κB-independent pathways in doxorubicin-resistant MCF-7 cells. These observations also prompt that furanodiene may be developed as a promising natural product for multidrug-resistant cancer therapy in the future.