Anticancer Ability Research Articles

2,3,5,4'-Tetrahydroxystilbene (TG1), a Novel Compound Derived from 2,3,5,4'-Tetrahydroxystilbene-2-O-β-D-glucoside (THSG), Inhibits Colorectal Cancer Progression by Inducing Ferroptosis, Apoptosis, and Autophagy.

Colorectal cancer (CRC) is one of the deadliest cancers worldwide and long-term survival is not guaranteed in metastatic disease despite current multidisciplinary therapies. A new compound 2,3,5,4'-Tetrahydroxystilbene (TG1), derived from THSG (2,3,5,4'-Tetrahydroxystilbene-2-O-β-D-Glucoside), has been developed, and its anticancer ability against CRC is verified in this study. HCT116, HT-29, and DLD-1 were treated with TG1 and the IC50 was measured using a sulforhodamine B assay. A Xenograft mouse model was used to monitor tumor growth. Apoptosis and autophagy, induced by TG1 in CRC cells, were examined. RNA-sequencing analysis of CRC cells treated with TG1 was performed to discover underlying pathways and mechanisms. The results demonstrated that treatment with TG1 inhibited CRC proliferation in vitro and in vivo and induced apoptotic cell death, which was confirmed by Annexin V-FITC/PI staining and Western blotting. Additionally, TG1 treatment increased the level of autophagy in cells. RNA-sequencing and GSEA analyses revealed that TG1 was associated with MYC and the induction of ferroptosis. Furthermore, the ferroptosis inhibitor Bardoxolone abrogated the cytotoxic effect of TG1 in CRC cells, indicating that ferroptosis played a crucial role in TG1-induced cytotoxicity. These findings suggest that TG1 might be a potential and potent compound for clinical use in the treatment of CRC by inhibiting proliferation and inducing ferroptosis through the MYC pathway.

Lipophilic Fe(III)-Complex with Potent Broad-Spectrum Anticancer Activity and Ability to Overcome Pt Resistance in A2780cis Cancer Cells.

Although iron is essential for all forms of life, it is also potentially toxic to cells as the increased and unregulated iron uptake can catalyze the Fenton reaction to produce reactive oxygen species (ROS), leading to lipid peroxidation of membranes, oxidation of proteins, cleavage of DNA and even activation of apoptotic cell death pathways. We demonstrate that Fe(hinok)3 (hinok = 2-hydroxy-4-isopropyl-2,4,6-cycloheptatrien-1-one), a neutral Fe(III) complex with high lipophilicity is capable of bypassing the regulation of iron trafficking to disrupt cellular iron homeostasis; thus, harnessing remarkable anticancer activity against a panel of five different cell lines, including Pt-sensitive ovarian cancer cells (A2780; IC50 = 2.05 ± 0.90 μM or 1.20 μg/mL), Pt-resistant ovarian cancer cells (A2780cis; IC50 = 0.92 ± 0.73 μM or 0.50 μg/mL), ovarian cancer cells (SKOV-3; IC50 = 1.23 ± 0.01 μM or 0.67 μg/mL), breast cancer cells (MDA-MB-231; IC50 = 3.83 ± 0.12 μM or 2.0 μg/mL) and lung cancer cells (A549; IC50 = 1.50 ± 0.32 μM or 0.82 μg/mL). Of great significance is that Fe(hinok)3 exhibits unusual selectivity toward the normal HEK293 cells and the ability to overcome the Pt resistance in the Pt-resistant mutant ovarian cancer cells of A2780cis.

Gemini nanoparticles-based quadruple therapy (GNQT) achieved effective tumor immunotherapy by comprehensive regulation of tumor microenvironment

Even though immune checkpoint blockade (ICB) therapy has advanced cancer immunotherapy greatly due to its quick development, and scientists have also tried a variety of combination therapies to further amplify the therapeutic impact, the therapeutic outcome is still limited because of the complex immunosuppressive microenvironment of tumor tissue. To improve the antitumor effect of immunotherapy, developing more comprehensive and effective tumor microenvironment regulation strategy is necessary. In this work, we prepared Gemini NPs composed of drug-loaded nanoparticles DI NPs (Doxorubicin and Ibrutinib were simultaneously encapsulated by PLG-g-mPEG) and gene-loaded nanoparticles PPD NPs (pSpam1 and pshPD-L1 were simultaneously encapsulated by PEI1.8k-RT), and proposed a Gemini nanoparticles-based quadruple therapy (GNQT). Compared with triple therapy and four-drug combination therapy, GNQT demonstrated comprehensive modulation of the tumor microenvironment and had exceptional anticancer ability in melanoma model without obvious toxicity. In addition, by establishing a persistent immunological memory effect, GNQT could also successfully prevent tumor lung metastasis in mice. The GNQT proposed here provided new insights into tumor immunotherapy and had important implications for the research of preclinical antitumor immunotherapy.

Enhancement of the Anticancer Ability of Natural Killer Cells through Allogeneic Mitochondrial Transfer.

An in vitro culture period of at least 2 weeks is required to produce sufficient natural killer (NK) cells for immunotherapy, which are the key effectors in hematological malignancy treatment. Mitochondrial damage and fragmentation reduce the NK cell immune surveillance capacity. Thus, we hypothesized that the transfer of healthy mitochondria to NK cells could enhance their anticancer effects. Allogeneic healthy mitochondria isolated from WRL-68 cells were transferred to NK cells. We evaluated NK cells' proliferative capacity, cell cycle, and cytotoxic capacity against various cancer cell types by analyzing specific lysis and the cytotoxic granules released. The relationship between the transferred allogenic mitochondrial residues and NK cell function was determined. After mitochondrial transfer, the NK cell proliferation rate was 1.2-fold higher than that of control cells. The mitochondria-treated NK cells secreted a 2.7-, 4.1-, and 5-fold higher amount of granzyme B, perforin, and IFN-γ, respectively, when co-cultured with K562 cells. The specific lysis of various solid cancer cells increased 1.3-1.6-fold. However, once allogeneic mitochondria were eliminated, the NK cell activity returned to the pre-mitochondrial transfer level. Mitochondria-enriched NK cells have the potential to be used as a novel solid cancer treatment agent, without the need for in vitro cytokine-induced culture.

ROS induction within 4T1 breast cancer cells by CuS NPs as chemodynamic agent

Minimally invasive and highly precise cancer cell death is a goal, and nanoformulations that can respond to the unique TME hold promise. This article describes the development of a nanoparticles (NPs) for chemodynamic treatment (CDT) to combat the cancer. As a consequence, CuS NPs cores are used as Fenton-like catalysts, while Alginate (Alg) is used as a stabilizer and template for entrapping and stabilizing Cu NPs. Here, Alg coated CuS NPs (CuS@Alg NPs) was synthesized via a green and facile method. To promote biocompatibility, Alg is added to the system. The malignant cells are killed by generated toxic hydroxyl radicals (·OH) using CuS@Alg NPs as a Fenton-like process catalyst. The effectiveness of NPs was assessed by MTT assay, live/dead cells staining, and ROS generation within cancer cells. Results not only confirmed ROS generation ability of CuS@Alg NPs within cells, but also show the anticancer ability of them. By CDT, the created smart nanoscale system showed remarkable effectiveness for breast cancer suppression.

Exploring Pyrrolo-Fused Heterocycles as Promising Anticancer Agents: An Integrated Synthetic, Biological, and Computational Approach.

Five new series of pyrrolo-fused heterocycles were designed through a scaffold hybridization strategy as analogs of the well-known microtubule inhibitor phenstatin. Compounds were synthesized using the 1,3-dipolar cycloaddition of cycloimmonium N-ylides to ethyl propiolate as a key step. Selected compounds were then evaluated for anticancer activity and ability to inhibit tubulin polymerization in vitro. Notably, pyrrolo[1,2-a]quinoline 10a was active on most tested cell lines, performing better than control phenstatin in several cases, most notably on renal cancer cell line A498 (GI50 27 nM), while inhibiting tubulin polymerization in vitro. In addition, this compound was predicted to have a promising ADMET profile. The molecular details of the interaction between compound 10a and tubulin were investigated through in silico docking experiments, followed by molecular dynamics simulations and configurational entropy calculations. Of note, we found that some of the initially predicted interactions from docking experiments were not stable during molecular dynamics simulations, but that configurational entropy loss was similar in all three cases. Our results suggest that for compound 10a, docking experiments alone are not sufficient for the adequate description of interaction details in terms of target binding, which makes subsequent scaffold optimization more difficult and ultimately hinders drug design. Taken together, these results could help shape novel potent antiproliferative compounds with pyrrolo-fused heterocyclic cores, especially from an in silico methodological perspective.

Inhibitory effect of N-oxalylglycine on gastric cancer cells

Some surveys have shown the possibility of controlling the growth of cancer cells by decreasing the content of 2OGoxygenase with NOG. This research aims to supply the blank of whether the anti-cancer ability of NOG exists in vitroand xenografted mice and how this ability is formed. Use human gastric cancer cell lines, SGC7901. They have broughtNOG, MTT, and cisplatin from different companies separately. Choose 60 male BALB/c Nude mice aged four weekswith an average weight of 15 – 20g as the experimental subject. Measure killing by MTT assay and tumor shrinkagein an SGC-7901 xenograft mouse and 2OG oxygenase by western blot. The possible results are: (1) NOG restrainsSGC7901 cells’ growth by inhibiting the abundance of 2OG oxygenase. (2) NOG can restrain the growth of SGC7901cells, but the principle differs from inhibiting the abundance of 2OG oxygenase. (3) NOG cannot restrain the growth ofSGC7901 cells.

Biofabrication of silver nanoparticles employing biomolecules of Paraclostridium benzoelyticum strain: Its characterization and their in-vitro antibacterial, anti-aging, anti-cancer and other biomedical applications.

The current study aims to utilize the bacteria Paraclostridium benzoelyticum strain 5610 to synthesize bio-genic silver nanoparticles (AgNPs). Biogenic AgNPs were thoroughly examined using various characterization techniques such as UV-spectroscopy, XRD, FTIR, SEM, and EDX. Synthesis of AgNPs was confirmed by UV-vis analysis resulting in absorption peak at 448.31 nm wavelength. The SEM analysis indicated the morphological characteristics and size of AgNPs which was 25.29 nm. The face centered cubic (FCC) crystallographic structure was confirmed by XRD. Furthermore, FTIR study affirmed the capping of AgNPs by different compounds found in biomass of the Paraclostridium benzoelyticum strain 5610. Later, EDX was used to determine the elemental composition with respective concentration and distribution. Additionally, in the current study the antibacterial, anti-inflammatory, antioxidant, anti-aging, and anti-cancer ability of AgNPs was assessed. The antibacterial activity of AgNPs was tested against four distinct sinusitis pathogens: Haemophilus in-fluenza, Streptococcus pyogenes, Moraxella catarrhalis and Streptococcus pneumonia. AgNPs shows significant inhibition zone against Streptococcus pyogenes 16.64 ± 0.35 followed by 14.32 ± 071 for Moraxella catarrhalis. Similarly, the antioxidant potential was found maximum (68.37 ± 0.55%) at 400 μg/mL and decrease (5.48 ± 0.65%) at 25 μg/mL, hence the significant antioxidant ability was observed. Furthermore, anti-inflammatory activity of AgNPs shows the strongest inhibitory action (42.68 ± 0.62%) for 15-LOX with lowest inhibition activity for COX-2 (13.16 ± 0.46%). AgNPs have been shown to exhibit significant inhibitory actions against the enzyme elastases AGEs (66.25 ± 0.49%), which are followed by AGEs of visperlysine (63.27 ± 0.69%). Furthermore, the AgNPs show high toxicity against HepG2 cell line which shows 53.543% reduction in the cell viability after 24 h of treatment. The anti-inflammatory activity demonstrated a potent inhibitory effect of the bio-inspired AgNPs. Overall, the biogenic AgNPs have the ability to be served for the treatments of anti-aging and also due to their anti-cancer, antioxidant abilities NPs may be a useful therapy choice for a variety of disorders including cancer, bacterial infections and other inflammatory diseases. Moreover, further studies are required in the future to evaluate their in vivo biomedical applications. HIGHLIGHTS: Biogenic synthesis of AgNPs using Paraclostridium benzoelyticum Strain for the first time. FTIR analysis confirmed capping of potent biomolecules which are of great use in applied field especially Nanomedicines. Notable antimicrobial activity against sinusitis bacteria and cytotoxic potential of synthesized AgNPs on in vitro basis produce a new idea shifting us to treat cancerous cell lines.

Non-oncology drug (meticrane) shows anti-cancer ability in synergy with epigenetic inhibitors and appears to be involved passively in targeting cancer cells.

Emerging evidence suggests that chemotherapeutic agents and targeted anticancer drugs have serious side effects on the healthy cells/tissues of the patient. To overcome this, the use of non-oncology drugs as potential cancer therapies has been gaining momentum. Herein, we investigated one non-oncology drug named meticrane (a thiazide diuretic used to treat essential hypertension), which has been reported to indescribably improve the therapeutic efficacy of anti-CTLA4 in mice with AB1 HA tumors. In our hypothesis-driven study, we tested anti-cancer potential meticrane in hematological malignance (leukemia and multiple myeloma) and liver cancer cell lines. Our analysis showed that: 1) Meticrane induced alteration in the cell viability and proliferation in leukemia cells (Jurkat and K562 cells) and liver cancer (SK-hep-1), however, no evidence of apoptosis was detectable. 2) Meticrane showed additive/synergistic effects with epigenetic inhibitors (DNMT1/5AC, HDACs/CUDC-101 and HDAC6/ACY1215). 3) A genome-wide transcriptional analysis showed that meticrane treatment induces changes in the expression of genes associated with non-cancer associated pathways. Of importance, differentially expressed genes showed favorable correlation with the survival-related genes in the cancer genome. 4) We also performed molecular docking analysis and found considerable binding affinity scores of meticrane against PD-L1, TIM-3, CD73, and HDACs. Additionally, we tested its suitability for immunotherapy against cancers, but meticrane showed no response to the cytotoxicity of cytokine-induced killer (CIK) cells. To our knowledge, our study is the first attempt to identify and experimentally confirm the anti-cancer potential of meticrane, being also the first to test the suitability of any non-oncology drug in CIK cell therapy. Beyond that, we have expressed some concerns confronted during testing meticrane that also apply to other non-oncology drugs when considered for future clinical or preclinical purposes. Taken together, meticrane is involved in some anticancer pathways that are passively targeting cancer cells and may be considered as compatible with epigenetic inhibitors.

Alternaria alternata (SDHY01/02), a fungus associated with Lamellodysidea herbacea: its anticancer potential and responsible constituent(s).

One of the biggest global causes of death is cancer. The side effects of currently available therapies have triggered the search for new drugs. The marine environment, with its vast biodiversity, including sponges, is a rich source of natural products with immense pharmaceutical potential. The aim of the study was to analyze the microbes associated with the marine sponge, Lamellodysidea herbacea, and explore them as resources for anticancer ability. This study includes the isolation of fungi from L. herbacea, and their evaluation for cytotoxic potential against human cancer cell lines such as A-549 (lung), HCT-116 (colorectal carcinoma), HT-1080 (Fibrosarcoma), and PC-3 (prostate) using MTT assay. This revealed that fifteen extracts showed significant anticancer ability (IC50 ≤ 20µg/mL), at least against one of the cell lines. Three extracts, SPG12, SPG19, and SDHY 01/02, were found significant in terms of anticancer activity, at least against three to four cell lines (IC50 values ≤ 20µg/mL). The fungus SDHY01/02 was identified by sequencing the internal transcribed spacer (ITS) region as Alternaria alternata. Its extract showed IC50 values < 10 µg/mL against all the tested cell lines and was further analysed through light and fluorescence microscopy. The extract of SDHY01/02 was active (lowest IC50 4.27µg/mL) against A549 cells in a dose-dependent manner and caused apoptotic cell death. Further, the extract was fractionated and analyzed the constituents by GC-MS (Gas Chromatography-Mass Spectrometry). Di-ethyl ether fraction revealed the constituents (having anticancer activity) such pyrrolo[1,2-a] pyrazine-1,4-dione, hexahydro-3-(2-methyl propyl); 4,5,6,7-tetrahydro-benzo[C]rhiophene-1-carboxylic acid cyclopropylamide; 17-pentatriacontene; 9,12-octadecadienoic acid (Z, Z)-, methyl ester; while DCM fraction contained Oleic acid, eicosyl ester. This is the first report of A. alternata with anticancer potential that has been isolated from the sponge L. herbacea, as far as we are aware.This A. alternatacan be exploited to get anticancer molecule(s) in the future.

Inulin enriched diet reinforces cancer immunosurveillance via γδ T cell activation

Abstract Gut microbiota is now recognized as a key player impacting the host’s anti-cancer immunosurveillance and ability to respond to immunotherapy. Its optimal modulation for preventive and therapeutic purposes is very appealing. Since diet is one of the most powerful modulators of the microbiota, nutritional interventions could be leveraged to improve host immunity. The present study aims to analyze the anticancer properties of inulin, a fiber known to promote bacteria described as immunostimulatory. The effects of inulin complementation were tested in mice fed an inulin-enriched diet for 2 weeks before tumor implantation. In the three tumor models used (melanoma, fibrosarcoma, and colorectal cancer), inulin consumption inhibited tumor growth by 80% compared to controls. Tumor-infiltrated immunity analysis showed that inulin triggers an enhanced Th1-polarized CD4 +CD8 +and γδ T cell-mediated antitumor response. In the gut, inulin consumption favored Bifidobacterium relative abundance, and strengthened gut immunity, by increasing the proportion of colonic IFNγ-producing γδ intra-epithelial T lymphocytes as well as the expression of genes involved in inflammation. In addition, we showed that the inulin-mediated anti-tumor effect is gut microbiota- and γδ T cell-dependent, as both antibiotic treatment and in vivo blocking of γδ TcR abrogate inulin efficacy. Overall, our data identified γδ T cells as a critical immune subset, mandatory for inulin-mediated antitumor immunity in vivo. This supports and rationalizes the use of a prebiotic approache as well as the development of immunotherapies targeting γδ T cells in cancer prevention and treatment. This work is supported by GEFLUC Dauphiné-Savoie, Ligue contre le Cancer Comité Isère, Ligue contre le Cancer Comité Savoie, Université Grenoble Alpes IDEX Initiatives de Recherche Stratégiques. Emilie Boucher is supported by a grant salary from the French Ministry of Higher Education, Research and Innovation.

Fucoidan/hyaluronic acid cross-linked zein nanoparticles loaded with fisetin as a novel targeted nanotherapy for oral cancer

Fisetin (FS) is an anticancer drug having potential role in oral tumors management. However, its clinical application is limited due to its hydrophobicity and instability. Bioactive polymers-based nanosystems have a great potential in cancer therapy. Herein, different biopolymers were selected for their anticancer activity and targeting ability for nanoparticles preparation namely; fucoidan (FU), zein (Zn) and hyaluronic acid (HA). The selected FS-loaded cross-linked Zn nanoparticles (ZFH) which contains HA& FU for Zn nanoparticles stabilization showed the most suitable particle size (196 ± 6.53 nm), mean surface net charge (−38.8 ± 1.47 mV) and entrapment efficiency (98 ± 1.2 %). This is the first study to utilize both HA &FU not only for stabilization but also for dual targeting effect due to their targeting ability to multiple tumor targets. In-vitro anticancer activity of ZHF revealed remarkable uptake by SCC-4 cells with significant cytotoxic action. Further, ZHF was appraised using 4-nitroquinoline 1-oxide (4-NQO)-induced oral cancer in-vivo; ZHF significantly reduced OSCC-specific serum biomarkers levels, histologic tumor grade and increased caspase-3 level. Moreover, potential of destroying two key tumor regulatory cells; TECs and CSCs, was evaluated using their specific markers. The elaborated ZFH nanoparticles could be considered as promising targeted nanotherapy for oral cancer treatment with enhanced efficacy and survival rate.

γ-tocotrienol regulates gastric cancer by targeting notch signaling pathway

BackgroundGastric cancer is a common cause of death from cancer and an important global health care issue. Consequently, there is an urgent need to find new drugs and therapeutic targets for the treatment of gastric cancer. Recent studies have shown that tocotrienols (T3) have significant anticancer ability in cancer cell lines. Our previous study found that γ-tocotrienol (γ-T3) induced apoptosis in gastric cancer cells. We further explored the possible mechanisms of γ-T3 therapy for gastric cancer.MethodsIn this study, we treated gastric cancer cells with γ-T3, collect and deposit the cells. γ-T3-treated gastric cancer cells group and untreated group were subjected to RNA-seq assay, and analysis of sequencing results.ResultsConsistent with our previous findings, the results suggest that γ-T3 can inhibit mitochondrial complexes and oxidative phosphorylation. Analysis reveals that γ-T3 has altered mRNA and ncRNA in gastric cancer cells. Significantly altered signaling pathways after γ-T3 treatment were enriched for human papillomavirus infection (HPV) pathway and notch signaling pathway. The same significantly down-regulated genes notch1 and notch2 were present in both pathways in γ-T3-treated gastric cancer cells compared to controls.ConclusionsIt is indicated that γ-T3 may cure gastric cancer by inhibiting the notch signaling pathway. To provide a new and powerful basis for the clinical treatment of gastric cancer.

Bioactivities of Kenaf Biomass Extracts: A Review

Kenaf or Hibiscus cannabinus is an annual herbaceous crop that grows well in temperate regions with high rainfall and abundant solar radiation. This Malvaceae member is famously known for its high-quality fibre that is directly retrieved from its dried stem materials and is useful in various industries, mainly in paper and pulp, bio-composite, textiles and manufacturing. With recent discoveries, kenaf can now be regarded as a multipurpose crop as its usage has been extended beyond its traditional applications, which include applications within the medicinal, pharmaceutical and food industries since its extracts possess several bioactivities that include anticancer, antimicrobial, antihypertensive, antidiabetic and antithrombotic abilities along with many more. The plant’s versatile applications and pharmaceutical activities come from its different plant parts such as its leaves, seeds, flowers and stems. This demonstrates that kenaf can also be safely regarded as a zero-waste crop, which is crucial for the sustainable development of any kenaf-based medicinal or therapeutic compounds. However, the biological properties of kenaf are still not known by many as industries mainly focus on the direct application of its fibre material. If this trend continues, the true potential of kenaf could be halted and undermined. Therefore, this paper aims to provide a concise overview of kenaf’s bioactivities that will hopefully provide better knowledge and understanding about this overlooked crop. This paper reviews the latest findings on kenaf’s bioactivities from its extracts that are retrieved from either its seeds, leaves, flowers or stems and provides additional information about its current status in Malaysia.

Radical Scavenging Is Not Involved in Thymoquinone-Induced Cell Protection in Neural Oxidative Stress Models.

Thymoquinone (TQ), an active compound from Nigella sativa seeds, is often described as a pharmacologically relevant compound with antioxidative properties, while the synthesis of TQ in the plant via oxidations makes it inapplicable for scavenging radicals. Therefore, the present study was designed to reassess the radical scavenging properties of TQ and explore a potential mode of action. The effects of TQ were studied in models with mitochondrial impairment and oxidative stress induced by rotenone in N18TG2 neuroblastoma cells and rotenone/MPP+ in primary mesencephalic cells. Tyrosine hydroxylase staining revealed that TQ significantly protected dopaminergic neurons and preserved their morphology under oxidative stress conditions. Quantification of the formation of superoxide radicals via electron paramagnetic resonance showed an initial increase in the level of superoxide radicals in the cell by TQ. Measurements in both cell culture systems revealed that the mitochondrial membrane potential was tendentially lowered, while ATP production was mostly unaffected. Additionally, the total ROS levels were unaltered. In mesencephalic cell culture under oxidative stress conditions, caspase-3 activity was decreased when TQ was administered. On the contrary, TQ itself tremendously increased the caspase-3 activity in the neuroblastoma cell line. Evaluation of the glutathione level revealed an increased level of total glutathione in both cell culture systems. Therefore, the enhanced resistance against oxidative stress in primary cell culture might be a consequence of a lowered caspase-3 activity combined with an increased pool of reduced glutathione. The described anti-cancer ability of TQ might be a result of the pro-apoptotic condition in neuroblastoma cells. Our study provides evidence that TQ has no direct scavenging effect on superoxide radicals.

Antioxidant, antibacterial, anti-inflammatory, and anticancer properties of Cinnamomum kanehirae Hayata leaves extracts

Bull Camphor tree (Cinnamomum kanehirae Hayata; CKH) (Lauraceae) is an endemic species in Taiwan. Its trunk is the main host of Taieanofugus camphoratus, traditional medical fungi. There are few research involving the functional properties and antibacterial activity of Cinnamomum kanehirae Hayata leaves (CKHL), although its abundant leaves. The purpose of the study was to investigate the effects of the different concentrations of ethanol solvents on the chemical compositions and biological activities of the CKHL extract (CKHLE). Furthermore, the antioxidant, antibacterial activity, anti-inflammatory, and anticancer ability of the extracts were tested. The results showed that the 50% ethanol CKHLE indicated the highest total polyphenols (TPC) and total flavonoids (TFC) (16.98 ± 0.18 mg GAE/g and 1.90 ± 0.04 mg QE/g, respectively) among the CKHLEs. The 50% ethanol CKHLE also indicated the best antioxidant performance in DPPH and ABTS+ free radical scavenging, reducing power, and ferric reducing antioxidant power (FRAP). The antioxidant performance of the four CKHLEs were exhibited in a dose-dependent manner. As well as, the 95% ethanol extract CKHLE indicated moderate antibacterial activity against Candida albicans, Escherichia coli, and Bacillus cereus. In terms of anti-inflammatory ability, all CKHLEs showed the best COX-2 inhibition at the concentration of 10 mg/mL. The 80% ethanol CKHLE reduced by 50.05% of NO production in Raw 264.7 cells compared to the control. The 80% and 95% CKHLEs also exhibited decreases in cell viability of colorectal cancer cells (C2BBe1) up to 94.64% and 93.99%, respectively, at the CKHLE’s concentration of 1000 μg/mL. These results demonstrated the different solvents affected the chemical compositions and biological activities (antibacterial, antioxidant, anti-inflammatory and anticancer activities) of CKHLE. Furthermore, the CKHLE are a potential source of healthy foods, bacteriostatic and non-steroidal anti-inflammatory drugs (NSAIDs) development.

Dipyridamole enhances the anti-cancer ability of aspirin against colorectal cancer by inducing apoptosis in an unfolded protein response-dependent manner.

Available evidence indicates that dipyridamole enhances the anti-thrombotic effects of aspirin for the prevention of secondary strokes. Aspirin is a well-known non-steroid anti-inflammatory drug. This anti-inflammatory property has turned aspirin into a potential drug for inflammation-related cancers such as colorectal cancer (CRC). Here, we aimed to explore whether the anti-cancer effect of aspirin against CRC could be improved by combined administration with dipyridamole. Population-based clinical data analysis was conducted to assess a possible therapeutic effect of combined dipyridamole and aspirin treatment in inhibiting CRC compared with either monotherapy. This therapeutic effect was further verified in different CRC mouse models, i.e. an orthotopic xenograft mouse model, an AOM/DSS mouse model, anApcmin/+ mouse model and a patient derived xenograft (PDX) mouse model. The in vitro effects of the drugs on CRC cells were tested using CCK8 and flow cytometry assays. RNA-Seq, Western blotting, qRT-PCR and flow cytometry were used to identify the underlying molecular mechanisms. We found that dipyridamole combined with aspirin had a better inhibitory effect on CRC than either monotherapy alone. The enhanced anti-cancer effect of the combined use of dipyridamole with aspirin was found to rely on the induction of an overwhelmed endoplasmic reticulum (ER) stress and subsequent pro-apoptotic unfolded protein response (UPR), which was different from the anti-platelet effect. Our data indicate that the anti-cancer effect of aspirin against CRC may be enhanced by combined administration with dipyridamole. In case further clinical studies confirm our findings, these may be repurposed as adjuvant agents.

Cultivation, nutritional value, bioactive compounds of morels, and their health benefits: A systematic review.

Morels are valuable mushrooms being used as foods and medical substances for a long history. The commonly cultivated morel species include M. eximia, M. importuna, and M. sextelata in China, M. conica and M. esculenta in the US. Morels' nutritional profile mainly consists of carbohydrates, proteins, fatty acids, vitamins, minerals, and organic acids, which are also responsible for its complex sensory attributes and health benefits. The bioactive compounds in morels including polysaccharides, phenolics, tocopherols, and ergosterols contribute to the anti-oxidative abilities, anti-inflammation, immunoprotection, gut health preservation, and anti-cancer abilities. This review depicted on the cultivation of morels, major bioactive compounds of different morel species both from fruit bodies and mycelia, and their health benefits to provide a comprehensive understanding of morels and support the future research and applications of morels as high-value functional food sources.

Citrus Honey Ameliorates Liver Disease and Restores Gut Microbiota in Alcohol-Feeding Mice.

Citrus honey (CH) is rich in nutrients that have a wide variety of biological functions, such as antibacterial, anti-inflammatory, and antioxidant activities, and which demonstrate therapeutic properties, such as anti-cancer and wound-healing abilities. However, the effects of CH on alcohol-related liver disease (ALD) and the intestinal microbiota remain unknown. This study aimed to determine the alleviating effects of CH on ALD and its regulatory effects on the gut microbiota in mice. In total, 26 metabolites were identified and quantified in CH, and the results suggested that the primary metabolites were abscisic acid, 3,4-dimethoxycinnamic acid, rutin, and two markers of CH, hesperetin and hesperidin. CH lowered the levels of aspartate aminotransferase, glutamate aminotransferase, and alcohol-induced hepatic edema. CH could promote the proliferation of Bacteroidetes while reducing the abundance of Firmicutes. Additionally, CH also showed some inhibitory effects on the growth of Campylobacterota and Turicibacter. CH enhanced the secretion of short-chain fatty acids (SCFAs), such as acetic acid, propionic acid, butyric acid, and valeric acid. Given its alleviating functions in liver tissue damage and its regulatory effects on the gut microbiota and SCFAs, CH could be a promising candidate for the therapeutic treatment of ALD.

Nobiletin Prevents Obesity-Related Complications and Neurological Disorders: An Overview of Preclinical and Clinical Studies

Nobiletin (NOB) chemically known as 5, 6, 7, 8, 3, 4-hexamethoxyflavone is a polymethoxylated flavonoid that is predominantly found in the peel of citrus fruits. Animal studies and a limited number of clinical trials suggest that NOB has multifunctional biological activities such as protection against obesity and obesity related cardiometabolic disorders, neuroprotection, antidiabetic, anticancer, anti-allergy, antioxidant, anti-inflammatory, and free radical scavenging abilities. NOB and its metabolites have also displayed antibacterial and antiviral properties and inhibition of hepatic lipogenesis. This review is intended to discuss the pharmacological actions and therapeutic potential of NOB and its metabolites in the prevention of obesity and obesity associated health complications. Evidence obtained from animal studies and a limited number of clinical trials suggest that NOB may be a promising candidate for the prevention of obesity and obesity related disorders as well as non-communicable diseases. Further studies are needed to understand the mechanism of action of NOB at the cellular, genetic, and molecular levels. Keywords: Nobiletin, obesity, cardiometabolic disorders, inhibition of hepatic lipogenesis, antiatherogenesis.