Inhibition of TBL1 cleavage alleviates doxorubicin-induced cardiomyocytes death by regulating the Wnt/ß-catenin signal pathway.

AIMS: Doxorubicin (DOX) is a widely used anthracycline anticancer agent; however, its irreversible effects on the heart can result in DOX-induced cardiotoxicity (DICT) after cancer treatment. Unfortunately, the pathophysiology of DICT has not yet been fully elucidated, and there are no effective strategies for its prevention or treatment. In this investigation, the novel role of transducin beta-like protein 1 (TBL1) in developing and regulating DICT was explored. METHODS AND RESULTS: We observed a reduction in TBL1 protein expression levels as well as cleavage events in the transplanted cardiac tissues of patients diagnosed with Dilated Cardiomyopathy (DCM) and DICT. It was revealed that DOX selectively induces TBL1 cleavage at caspase-3 preferred sites-D125, D136, and D215. Interestingly, overexpression of the uncleaved TBL1 mutant (TBL1uclv) variant reduced apoptosis, effectively preventing DOX-induced cell death. We confirmed that cleaved TBL1 cannot form a complex with ß-catenin. As a result, Wnt reporter activity, and Wnt target gene expression collectively indicate a decrease in Wnt/ß-catenin signaling, leading to DICT progression. Furthermore, the cleaved TBL1 triggered DOX-induced abnormal electrophysiological features and disrupted calcium homeostasis. However, these effects were improved in TBL1uclv-overexpressing human-induced pluripotent stem cell-derived cardiomyocytes. Finally, in a DICT mouse model, TBL1uclv overexpression inhibited the DICT-induced reduction of cardiac contractility and collagen accumulation, ultimately protecting cardiomyocytes from cell death. CONCLUSIONS: Our findings reveal that the inhibition of TBL1 cleavage not only mitigates apoptosis but also enhances cardiomyocyte function, even in the context of DOX administration. Consequently, this study's results suggest that inhibiting TBL1 cleavage may be a novel strategy to ameliorate DICT.

The Bioactivity and Phytochemicals of Muscari comosum (Leopoldia comosa), a Plant of Multiple Pharmacological Activities.

Leopoldia comosa (LC), popularly known as Muscari comosum, spontaneously grows in the Mediterranean region and its bulbs are used as a vegetable. Traditionally, they are also used to treat various diseases and conditions, which has inspired the study of the pharmacological activities of different parts of LC. These studies revealed the numerous biological properties of LC including antioxidant, anti-inflammatory, anti-diabetes, anti-obesity, anti-cancer, anti-Alzheimer's disease, antibacterial, and immune stimulant. High antioxidant activity compared to other non-cultivated plants, and the potential role of antioxidant activity in other reported activities make LC an excellent candidate to be developed as an antioxidant plant against important associated diseases. The presence of a diverse class of phytochemicals (n = 85), especially flavonoids and homoisoflavones, in LC, also imparts significance to the nutraceutical candidature of the plant. However, limited animal studies and the lack of a directional approach have limited the further design of effective clinical studies for the development of LC. The current study is the first attempt to comprehensively compile information regarding the phytochemicals and pharmacological activities of LC, emphasize the targets/markers targeted by LC, important in other activities, and also highlight the current gaps and propose possible bridges for the development of LC as a therapeutic and/or supplement against important diseases.

An Update on the Chemical Constituents and Biological Properties of Selected Species of an Underpinned Genus of Red Algae: Chondrus.

Macroalgae, particularly red seaweeds, have attracted significant attention due to their economic and health benefits. Chondrus, a red algae genus, despite its economic importance, seems to be undervalued. Among all its species, Chondrus crispus has been meticulously documented for its biological properties, and little is known about other species. No comprehensive review of the biological properties of this genus has been acknowledged. Thus, this review aimed to summarize the available information on the chemical constituents and biological properties of a few selected species, including Chondrus crispus, Chondrus ocellatus, Mazzaella canaliculata, and Chondrus armatus. We compiled and discovered that the genus is offering most of the important health-promoting benefits evidenced from in vitro and in vivo studies focused on antimicrobial, immunomodulation, neuroprotection, anti-atopic, anti-inflammatory, anti-viral, anti-diabetic, cytoprotective, antioxidant, anti-coagulation, nephroprotective, anti-tumor, and anti-venom activity, which speaks about the potential of this genus. Data on clinical studies are limited. Further, around 105 chemical constituents have been reported from Chondrus spp. Given its significance, further investigation is warranted, in the form of meticulously planned cell, animal, and clinical studies that concentrate on novel health-enhancing endeavors, in order to unveil the full potential of this genus. The review also outlines challenges and future directions.

Comparative study on estrogen receptor alpha dimerization and transcriptional activity of parabens.

Parabens are used as preservatives in various household products, including oral products, cosmetics, and hair/body washes. In recent years, the widespread use of parabens has raised concerns due to the potential health risks associated with their estrogenic effects. In the present study, we evaluated and compared the estrogenic activity of parabens using two cell-based in vitro tests: (1) bioluminescence resonance energy transfer (BRET)-based estrogen receptor alpha (ERα) dimerization using HEK293 cells that were stably transfected with ERα-fused NanoLuc luciferase (Nluc) and HaloTag (HT) expression vector, and (2) stably transfected transcriptional activation (STTA) assays using ERα-HeLa9903 cells. The following parabens were tested using the BRET-based ERα dimerization assay and showed estrogenic activity (PC20 values): methyl paraben (MP, 5.98 × 10-5 M), ethyl paraben (EP, 3.29 × 10-5 M), propylparaben (PP, 3.09 × 10-5 M), butyl paraben (BP, 2.58 × 10-5 M), isopropyl paraben (IsoPP, 1.37 × 10-5 M), and isobutyl paraben (IsoBP, 1.43 × 10-5 M). Except MP, all other parabens tested using the STTA assay also showed estrogenic activity: EP, 7.57 × 10-6 M; PP, 1.18 × 10-6 M; BP, 3.02 × 10-7 M; IsoPP, 3.58 × 10-7 M; and IsoBP, 1.80 × 10-7 M. Overall, EP, PP, BP, IsoPP, and IsoBP tested positive for estrogenic activity using both assays. These findings demonstrate that most parabens, albeit not all, induce ERα dimerization and possess estrogenic activity.

Cyanidin-3-O-glucoside protects the brain and improves cognitive function in APPswe/PS1ΔE9 transgenic mice model.

Cyanidin-3-O-glucoside (C3G) is a natural anthocyanin with antioxidant, anti-inflammatory, and antitumor properties. However, as the effects of C3G on the amyloidogenic pathway, autophagy, tau phosphorylation, neuronal cell death, and synaptic plasticity in Alzheimer's disease models have not been reported, we attempted to investigate the same in the brains of APPswe/PS1ΔE9 mice were analyzed. After oral administration of C3G (30 mg/kg/day) for 16 weeks, the cortical and hippocampal regions in the brains of APPswe/PS1ΔE9 mice were analyzed. C3G treatment reduced the levels of soluble and insoluble Aß (Aß40 and Aß42) peptides and reduced the protein expression of the amyloid precursor protein, presenilin-1, and ß-secretase in the cortical and hippocampal regions. And C3G treatment upregulated the expression of autophagy-related markers, LC3B-II, LAMP-1, TFEB, and PPAR-α and downregulated that of SQSTM1/p62, improving the autophagy of Aß plaques and neurofibrillary tangles. In addition, C3G increased the protein expression of phosphorylated-AMPK/AMPK and Sirtuin 1 and decreased that of mitogen-activated protein kinases, such as phosphorylated-Akt/Akt and phosphorylated-ERK/ERK, thus demonstrating its neuroprotective effects. Furthermore, C3G regulated the PI3K/Akt/GSK3ß signaling by upregulating phosphorylated-Akt/Akt and phosphorylated-GSK3ß/GSK3ß expression. C3G administration mitigated tau phosphorylation and improved synaptic function and plasticity by upregulating the expression of synapse-associated proteins synaptophysin and postsynaptic density protein-95. Although the potential of C3G in the APPswe/PS1ΔE9 mouse models has not yet been reported, oral administration of the C3G is shown to protect the brain and improve cognitive behavior.

Carbon Dots for the Treatment of Inflammatory Diseases: An Appraisal of In Vitro and In Vivo Studies.

In recent decades, several studies demonstrating various applications of carbon dots (C-dots), including metal sensing, bioimaging, pH sensing, and antimicrobial activities, have been published. Recent developments have shifted this trend toward biomedical applications that target various biomarkers relevant to chronic diseases. However, relevant developments and research results regarding the anti-inflammatory properties of C-dots against inflammation-associated diseases have not been systematically reviewed. Hence, this review discusses the anti-inflammatory effects of C-dots in in vivo and in vitro models of LPS-induced inflammation, gout, cartilage tissue engineering, drug-induced inflammation, spinal cord injury, wound healing, liver diseases, stomach cancer, gastric ulcers, acute kidney and lung injury, psoriasis, fever or hypothermia, and bone tissue regeneration. The compiled studies demonstrate the promising potential of C-dots as anti-inflammatory agents for the development of new drugs.

Biogenic silver NPs alleviate LPS-induced neuroinflammation in a human fetal brain-derived cell line: Molecular switch to the M2 phenotype, modulation of TLR4/MyD88 and Nrf2/HO-1 signaling pathways, and molecular docking analysis.

Silver nanoparticles (AgNPs) have inconsistent findings against inflammation. Although a wealth of literature on the beneficial effects of green-synthesized AgNPs has been published, a detailed mechanistic study of green AgNPs on the protective effects against lipopolysaccharide (LPS)-induced neuroinflammation using human microglial cells (HMC3) has not yet been reported. For the first time, we studied the inhibitory effect of biogenic AgNPs on inflammation and oxidative stress induced by LPS in HMC3 cells. X-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy, and transmission electron microscopy were used to characterize AgNPs produced from honeyberry. Co-treatment with AgNPs significantly reduced mRNA expressions of inflammatory molecules such as interleukin (IL)-6 and tumor necrosis factor-α, while increasing the expressions of anti-inflammatory markers such as IL-10 and transforming growth factor (TGF)-ß. HMC3 cells were also switched from M1 to M2, as shown by lower expression of M1 markers such as cluster of differentiation (CD)80, CD86, and CD68 and higher expression of M2 markers such as CD206, CD163, and triggering receptors expressed on myeloid cells (TREM2). Furthermore, AgNPs inhibited LPS-induced toll-like receptor (TLR)4 signaling, as evidenced by decreased expression of myeloid differentiation factor 88 (MyD88) and TLR4. In addition, AgNPs reduced the production of reactive oxygen species (ROS) and enhanced the expression of nuclear factor-E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), while decreasing the expression of inducible nitric oxide synthase. The docking score of the honeyberry phytoconstituents ranged from -14.93 to - 4.28 KJ/mol. In conclusion, biogenic AgNPs protect against neuroinflammation and oxidative stress by targeting TLR4/MyD88 and Nrf2/HO-1 signaling pathways in a LPS-induced in vitro model. Biogenic AgNPs could be utilized as potential nanomedicine against LPS-induced inflammatory disorders.

Pharmacological Activities of Mogrol: Potential Phytochemical against Different Diseases.

Recently, mogrol has emerged as an important therapeutic candidate with multiple potential pharmacological properties, including neuroprotective, anticancer, anti-inflammatory, antiobesity, antidiabetes, and exerting a protective effect on different organs such as the lungs, bone, brain, and colon. Pharmacokinetic studies also highlighted the potential of mogrol as a therapeutic. Studies were also conducted to design and synthesize the analogs of mogrol to achieve better activities against different diseases. The literature also highlighted the possible molecular mechanism behind pharmacological activities, which suggested the role of several important targets, including AMPK, TNF-α, and NF-κB. These important mogrol targets were verified in different studies, indicating the possible role of mogrol in other associated diseases. Still, the compilation of pharmacological properties, possible molecular mechanisms, and important targets of the mogrol is missing in the literature. The current study not only provides the compilation of information regarding pharmacological activities but also highlights the current gaps and suggests the precise direction for the development of mogrol as a therapeutic against different diseases.

Development and Validation of a Food Frequency Questionnaire for Evaluating the Nutritional Status of Patients with Cancer.

Patients with cancer need to maintain proper nutritional status to overcome cancer, alleviate the side effects of chemotherapy, and prevent a recurrence. As such, it is necessary to manage nutritional status. This study aimed to develop a dish-based semi-quantitative food frequency questionnaire (FFQ) to evaluate the nutritional status of patients with cancer and assess the validity of the FFQ. A total of 109 dish items were selected through contribution and variability analyses using the 2016-2018 Korea National Health and Nutrition Examination Survey data. The FFQ was validated against the average 3-day dietary records of 100 patients with cancer. Pearson correlation coefficients and quartile agreements between FFQ and 3-day dietary records were calculated for intake of energy, macronutrients, and micronutrients. Age and energy-adjusted Pearson correlation coefficients ranged from 0.20 (iron) to 0.54 (potassium). The percentage of participants who were classified into the same or adjacent quartile between the FFQ and the 3-day dietary record ranged from 68% (protein) to 81% (energy, dietary fiber). The results suggest that the FFQ is an appropriate tool for assessing nutritional status in Korean cancer patients.

Recent Clinical Advances on Long Non-Coding RNAs in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a more aggressive type of breast cancer due to its heterogeneity and complex molecular mechanisms. TNBC has a high risk for metastasis, and it is difficult to manage clinical conditions of the patients. Various investigations are being conducted to overcome these challenges using RNA, DNA, and proteins for early diagnosis and treatment. Recently, long non-coding RNAs (lncRNAs) have emerged as a novel target to treat the multistep process of TNBC. LncRNAs regulate epigenetic expression levels, cell proliferation and apoptosis, and tumour invasiveness and metastasis. Thus, lncRNA-based early diagnosis and treatment options could be helpful, especially for patients with severe TNBC. lncRNAs are expressed in a highly specific manner in cells and tissues and are involved in TNBC progression and development. lncRNAs could be used as sensitive and specific targets for diagnosis, treatment, and monitoring of patients with TNBC. Therefore, the exploration of novel diagnostic and prognostic biomarkers is of extreme importance. Here, we discuss the molecular advances on lncRNA regulation of TNBC and lncRNA-based early diagnosis, treatment, and drug resistance.

Pharmacological Properties of Shionone: Potential Anti-Inflammatory Phytochemical against Different Diseases.

Shionone is a triterpenoid that is the primary constituent of an important ancient Chinese medicine named Radix Asteris. It has emerged as an attractive candidate against different important diseases, including interstitial cystitis, colitis, cancer, Parkinson's disease, and urinary tract infections, and was found to have a protective effect on multiple organs, including the colon, kidneys, lungs, brain, and bladder. The anti-inflammation activity of shionone may be considered an important property that imparts the positive health outcomes of shionone. Important molecular targets and markers such as TNF-α, STAT3, NLRP3, and NF-κB were also found to be targeted by shionone and were verified in different diseases. This suggests the possible potential of shionone against other diseases associated with these targets. Pharmacokinetic studies also support the therapeutic potential of shionone and provide the initial track that may be pursued for its development. Yet, the compilation of the pharmacological activities of shionone and its important genes and pathway targets are absent in the existing literature, which would direct its development as a therapeutic and/or supplement. Hence, the present review provides a compilation of information concerning pharmacological activities, highlights the existing holes, and proposes a specific direction for the expansion of shionone as a therapeutic against different diseases and conditions.

Antioxidant Activity of Urtica dioica: An Important Property Contributing to Multiple Biological Activities.

Urtica dioica (UD) is a multi-functional plant known to be used as both food and medicine from ancient times. The plant has the potential to be used as a fertilizer and for biological pest control. It is also used in textile and related industries for its quality fibers. In the recent past, the plant has received great attention for its numerous important biological activities and food applications. The antioxidant activity of UD is the crucial factor supporting its important biological activities, such as anticancer, antidiabetic and anti-inflammatory properties. The antioxidant activity of UD is also found to be protective in different organs, including the brain, liver, lungs, kidney, ovary, and uterus, and may also be protective against diseases associated with these organs. Few clinical studies have endorsed the antioxidant potential of UD in patients. The current work is an attempt to comprehensively compile and discuss the antioxidant activity of UD from in vitro, in vivo and human studies. The insights of the current study would be helpful in getting a panoramic view of the antioxidant potential of UD, and provide direction for optimizing and developing it for therapeutic applications against important diseases and conditions in the near future.

Stevia and Stevioside Attenuate Liver Steatosis through PPARα-Mediated Lipophagy in db/db Mice Hepatocytes.

Lipophagy, a type of autophagy that breaks down lipid droplets, is essential in the regulation of intracellular lipid accumulation and intracellular free fatty acid levels in numerous organisms and metabolic conditions. We investigated the effects of Stevia rebaudiana Bertoni (S), a low-calorie sweetener, and stevioside (SS) on hepatic steatosis and autophagy in hepatocytes, as well as in db/db mice. S and SS reduced the body and liver weight and levels of serum triglyceride, total cholesterol, and hepatic lipogenic proteins. In addition, S and SS increased the levels of fatty acid oxidase, peroxisome proliferator-activated receptor alpha (PPARα), and microtubule-associated protein light chain 3 B but decreased that of sequestosome 1 (p62) in the liver of db/db mice. Additionally, Beclin 1, lysosomal associated membrane protein 1, and phosphorylated adenosine monophosphate-activated protein kinase protein expression was augmented following S and SS treatment of db/db mice. Furthermore, the knockdown of PPARα blocked lipophagy in response to SS treatment in HepG2 cells. These outcomes indicate that PPARα-dependent lipophagy is involved in hepatic steatosis in the db/db mouse model and that SS, a PPARα agonist, represents a new therapeutic option for managing associated diseases.

Clinical updates on tyrosine kinase inhibitors in HER2-positive breast cancer.

Breast cancer (BC) is caused by epigenetic modifications and genetic heterogeneity and exhibits various histological feature. HER2+ (Human epidermal growth factor receptor 2) is a more aggressive type of breast cancer, diagnosis and prognosis are difficult for HER2+ BC. Anti-HER2+ inhibitors have been effectively used for patient treatment. High mortality rate is reported in HER2+ BC, due to availability of limited therapeutic options. Despite advances in systemic medications to treat metastatic breast cancer (MBC), HER2-positive MBC is still challenging for patients and treating clinicians. The clinical characteristics of the disease have changed after treatment with HER2-targeted therapy. Various types of Tyrosine kinase inhibitors (TKIs) have been developed to treat patients with HER2+ BC including afatinib, lapatinib, neratinib, tucatinib, and pyrotinib, have been developed as HER2-targeted therapies. The antibody-drug conjugates adotrastuzumab, emtansine, famtrastuzumab, and deruxtecan, as well as the anti-HER2 monoclonal antibody pertuzumab are used in both early-stage and metastatic situations, either alone or in conjunction with chemotherapy and other HER2-targeting therapies. The emergence of drug resistance in anti-HER2 therapies has been observed. To overcome drug resistance and limited efficacy in current treatment options, nano formulations can be used in patients with HER2+ BC treatment. Anti-HER2 ligands can be used in various nano formulations to target HER2 receptors. Here we will discuss, targeted TKIs in patients with HER2+ BC, clinical studies of HER2+ targeted TKIs, mechanisms of resistance to HER2-directed therapies with new implications of TKIs in HER2+ MBC (metastatic breast cancer) and anti-HER2 ligand in various nano formulations to target HER2 receptors.

Mulberry Leaf Supplements Effecting Anti-Inflammatory Genes and Improving Obesity in Elderly Overweight Dogs.

Overweight and obesity, associated with various health complications, refer to abnormal or excessive fat accumulation conditions that harm health. Like humans, obesity is a growing problem in dogs, which may increase the risk of serious diseases such as diabetes and cancer. Mulberry leaf has shown potential anti-obesity and anti-diabetes effects in several studies. Our research studied the impact of mulberry leaf supplements in healthy old overweight dogs for 12 weeks. Blood and fecal samples were collected from the dogs before and after treatment for different analyses, including whole transcriptome and gut microbiome analysis. The Body Condition Score (BCS) and blood glucose levels were significantly decreased in all mulberry treatment groups, which justifies the anti-obesity effect of mulberry leaf in dogs. Throughout the whole transcriptome study, the downregulation of PTX3 and upregulation of PDCD-1, TNFRSF1B, RUNX3, and TICAM1 genes in the high mulberry group were found, which have been associated with anti-inflammatory effects in the literature. It may be an essential gene expression mechanism responsible for the anti-inflammatory and, subsequently, anti-obesity effects associated with mulberry leaf treatment, as confirmed by real-time polymerase chain reaction analysis. In microbiome analysis, Papillibacter cinnamivorans, related to the Mediterranean diet, which may cause anti-inflammatory effects, were abundant in the same treatment group. Further studies may be required to establish the gene expression mechanism and role of abundant bacteria in the anti-obesity effect of mulberry supplements in dogs. Overall, we propose mulberry leaves as a portion of food supplements for improving blood glucose levels and the anti-inflammation of blood in companion dogs.

Effects of Ginger Intake on Chemotherapy-Induced Nausea and Vomiting: A Systematic Review of Randomized Clinical Trials.

Nausea and vomiting are the most common side effects of chemotherapy. They must be managed because they can increase the risk of malnutrition in patients, which can adversely affect treatment. The objective of this study was to evaluate the effect of ginger supplementation as an adjuvant treatment for alleviating chemo We checked. therapy-induced nausea and vomiting (CINV). This study searched for randomized controlled trials (RCTs) related to ginger supplement intake for CINV in three electronic databases (i.e., Medline (PubMed), Embase, and Web of Science). The search period ranged from each database's first date of service to 5 November 2021. Two investigators independently performed abstract screenings, full-text screenings, data extraction, and risk of bias analyses (ROB). The Cochrane ROB tool was used for the assessment of ROB. This study systematically reviewed 23 RCTs. The effects of ginger supplementation were compared to those of placebo or antiemetic agents. This study conducted a meta-analysis after classifying the effects of ginger supplementation on acute and delayed CINV into subgroups due to the clinical heterogeneity between these RCTs. The results showed that the incidence of acute nausea (p = 0.53), the incidence of delayed nausea (p = 0.31), the incidence of acute vomiting (p = 0.09), and the incidence of delayed vomiting (p = 0.89) were not significantly different between the ginger supplement intake group and the control group. However, it was found that the ginger supplement intake group, which took not more than 1 g of ginger supplementation per day for above four days, had significantly less acute vomiting than the control group (OR 0.30; 95% CI 0.12 to 0.79; p = 0.02; I2 = 36%). Ginger supplementation may reduce the incidence of acute chemotherapy-induced vomiting. However, this study could not confirm the effects of ginger supplementation on the incidence of chemotherapy-induced nausea and delayed vomiting. Therefore, it will be necessary to conduct additional studies with sufficient sample sizes using high-quality RCTs to evaluate the effects of ginger supplementations based on the results of this study.

Differences in health behavior and nutrient intake status between diabetes-aware and unaware Korean adults based on the Korea national health and nutrition examination survey 2016-18 data: A cross-sectional study.

Background: The aim of this study was to investigate the nutritional intakes and treatment regimens of Korean patients with type 2 diabetes who were aware of their condition. Methods: Participants (n = 16582) aged ≥ 19 years from the 2016-18 National Health and Nutrition Survey were divided into diabetes-aware and unaware groups and the variables were compared. Results: Among 1,906 (11.5%) diabetic adults, 1,433 (75.2%) were aware of their condition; 130 (9.1%) had nutrition education, and 1,340 (93.5%) were in the diabetes-aware treatment group. The diabetes-aware group had higher average age (P < 0.0001) and lower average BMI (P = 0.0015) than the unaware group. Intake of total fat (P = 0.0034), saturated fatty acids (P = 0.0021), riboflavin (P = 0.0035) and niacin (P = 0.0228) was significantly higher in the unaware group than in the diabetes-aware group, after adjusting energy intake for age and sex. Current smoking (P = 0.0046) and heavy drinking (P < 0.0001) rates were higher in the unaware group, whereas fiber intake (P = 0.0054) was lower in the unaware group. Higher levels of glycated hemoglobin were found in the group treated for diabetes (7.2%) than in the no-treatment (6.8%) group (P = 0.0048). Diabetes control was significantly better in the high income group. Conclusions: There is a need to strengthen nutritional education to prevent diabetes and improve the health status of diabetic patients in Korea.

Frankincense oil-loaded nanoemulsion formulation of paclitaxel and erucin: A synergistic combination for ameliorating drug resistance in breast cancer: In vitro and in vivo study.

Nanoformulation-based combinational drug delivery systems are well known to overcome drug resistance in cancer management. Among them, nanoemulsions are well-known and thermodynamically stable drug delivery systems suitable for carrying hydrophobic drugs and phytoconstituents to tackle drug-resistant cancers. In the present study, we have investigated the effect of paclitaxel in combination with erucin (natural isothiocyanate isolated from the seeds of Eruca sativa) loaded in the frankincense oil-based nanoemulsion formulation. The choice of frankincense oil for the current study was based on reported research investigations stating its magnificient therapeutic potential against breast cancer. Optimized nanoemulsion of paclitaxel (PTX) and erucin (ER) combination (EPNE) provided sustained release and exhibited enhanced cytotoxicity towards human epithelial breast cancer cells (T-47D) as compared to individual ER and PTX. EPNE was further assessed for its antitumor activity in the 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer mice model. EPNE significantly decreased the levels of hepatic and renal parameters along with oxidative stress in breast cancer mice. Furthermore, EPNE also showed decreased levels of inflammatory cytokines TNF-α, IL-6. Histopathological examinations revealed restoration of the tumorous breast to normal tissues in EPNE-treated breast cancer mice. Therefore, EPNE can act as a viable lead and therapeutic option for drug-resistant breast cancer.

Nuciferine attenuates lipopolysaccharide-stimulated inflammatory responses by inhibiting p38 MAPK/ATF2 signaling pathways.

Nuciferine, isolated from Nelumbo nucifera (commonly known as lotus) leaves, has been shown to have beneficial effects, including antioxidant, anti-obesity, anti-diabetic, and anti-inflammatory properties. However, little is known about the mechanism of nuciferine action on the inflammatory response. This study aimed to investigate the anti-inflammatory effects of nuciferine and its underlying molecular mechanisms in lipopolysaccharide (LPS)-stimulated murine macrophages. In this study, nuciferine reduced LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production and mRNA expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2. Nuciferine also decreased the production of pro-inflammatory cytokines such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α. Furthermore, nuciferine inhibited the LPS-mediated transcriptional activity of nuclear factor (NF)-κB and activator protein (AP)-1, and the nuclear translocation of NF-κB p65 and activating transcription factor 2 (ATF2), an AP-1 subunit. Nuciferine also decreased the phosphorylation of IκB kinase (IKK), inhibitor of NF-κB (IκB), NF-κB, mitogen-activated protein kinase 3 (MKK3), MKK6, p38 mitogen-activated protein kinase (MAPK), and ATF2. Overall, our findings suggest that nuciferine may exert anti-inflammatory effects in LPS-induced macrophages by inhibiting the NF-κB and p38 MAPK/ATF2 signaling pathways.

Anti-Inflammatory Activity of Bilberry (Vaccinium myrtillus L.).

Inflammation is important in the pathogenesis of several chronic diseases. The anti-inflammatory properties of berries have been investigated but the anti-inflammatory activity of bilberry has received little attention and a detailed review is yet to be published. Therefore, we compiled information on the phytochemicals of bilberry and preclinical and clinical studies of its anti-inflammatory properties. The review was based on studies from 2007 to date. Phytoconstituents of bilberries were phenolic acids, organic acids, anthocyanins, coumarins, flavonols, flavanols, tannins, terpenoids, and volatile chemicals. Data from cell and animal model studies show that bilberry has an anti-inflammatory effect by lowering tumor necrosis factor-α, interleukin (IL)-6, and IL-1ß expression, inducing nitric oxide synthases and cyclooxygenases, and altering the nuclear factor kappa B and Janus kinase-signal transducer and activator of transcription signaling pathways. Bilberry supplementation as fruits (frozen, processed, and whole), juices, and anthocyanins reduced levels of inflammatory markers in most clinical studies of metabolic disorders. Therefore, bilberry may be useful for the prevention and treatment of chronic inflammatory disorders.