Assessing Anticancer Properties of PEGylated Platinum Nanoparticles on Human Breast Cancer Cell lines using in-vitro Assays.

This study describes the in-vitro cytotoxic effects of PEG-400 (Polyethylene glycol-400)-capped platinum nanoparticles (PEGylated Pt NPs) on both normal and cancer cell lines. Structural characterization was carried out using X-ray diffraction and Raman spectroscopy with an average crystallite size 5.7 nm, and morphological assessment using Scanning electron microscopy (SEM) revealed the presence of spherical platinum nanoparticles. The results of energy-dispersive X-ray spectroscopy (EDX) showed a higher percentage fraction of platinum content by weight, along with carbon and oxygen, which are expected from the capping agent, confirming the purity of the platinum sample. The dynamic light scattering experiment revealed an average hydrodynamic diameter of 353.6 nm for the PEGylated Pt NPs. The cytotoxicity profile of PEGylated Pt NPs was assessed on a normal cell line (L929) and a breast cancer cell line (MCF-7) using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The results revealed an IC50 of 79.18 µg/ml on the cancer cell line and non-toxic behaviour on the normal cell line. In the dual staining apoptosis assay, it was observed that the mortality of cells cultured in conjunction with platinum nanoparticles intensified and the proliferative activity of MCF-7 cells gradually diminished over time in correlation with the increasing concentration of the PEGylated Pt NPs sample. The in vitro DCFH-DA assay for oxidative stress assessment in nanoparticle-treated cells unveiled the mechanistic background of the anticancer activity of PEGylated platinum nanoparticles as ROS-assisted mitochondrial dysfunction.

Antioxidant and Anti-Inflammatory Capacities of Three Dry Bean Varieties after Cooking and In Vitro Gastrointestinal Digestion.

The present study delved into the chemical composition, antioxidant, and anti-inflammatory properties of three dry edible beans: Black (BL), Great Northern (GN), and Pinto (PN). The beans were soaked, cooked, and subjected to in vitro gastrointestinal (GI) digestion. BL bean exhibited significantly higher gastric (42%) and intestinal (8%) digestion rates. Comparative assessment of soluble GI-digested fractions (<3 kDa) revealed that the GN bean exhibited the highest abundance of dipeptides (P < 0.05). The BL bean fraction displayed a 4-fold increase in tripeptides (P < 0.05). Both BL and PN bean fractions are high in essential free amino acids, flavonols, and derivatives of hydroxybenzoic acid when compared to the GN bean. All the beans exhibited the ability to mitigate TNF-α-induced pro-inflammatory signaling; however, the BL bean fraction was the most effective at lowering AAPH-induced oxidative stress in HT-29 cells, followed by the GN bean (P < 0.05). In contrast, a low antioxidant effect was observed with PN beans.

Mechanism of DYRK1a in myocardial ischemia-reperfusion injury by regulating ferroptosis of cardiomyocytes.

This study aimed to explore the role and mechanism of DYRK1a regulating ferroptosis of cardiomyocytes during myocardial ischemia-reperfusion injury (MIRI). H9c2 cells treated with oxygen-glucose deprivation/reoxygenation (OGD/R) were used as MIRI cell models and transfected with sh-DYRK1a or/and erastin. Cell viability, apoptosis, and DYRK1a mRNA/protein expression were measured accordingly. The levels of reactive oxygen species (ROS), iron, malondialdehyde (MDA), and glutathione (GSH) were determined. The expression of ferroptosis-related proteins (GPX4, SLC7A11, ACSL4, and TFR1) was detected using western blotting. The MIRI rat model was established to explore the possible role of DYRK1a suppression in cell injury and ferroptosis. OGD/R cells showed elevated mRNA and protein expression for DYRK1a. OGD/R cells transfected with sh-DYRK1a showed elevated cell viability, GSH content, increased GPX4 and SLC7A11 expression, suppressed iron content, MDA, ROS, ACSL4, and TFR1 expression, and reduced apoptosis rate, whereas co-transfection of sh-DYRK1a with erastin reversed the attenuation of sh-DYRK1a on MIRI. The suppressive effect of sh-DYRK1a on MI/R injury was confirmed in an MIRI rat model. DYRK1a mediates ferroptosis of cardiomyocytes to deteriorate MIRI progression.

Short-chain fatty acids reprogram metabolic profiles with the induction of reactive oxygen species production in human colorectal adenocarcinoma cells.

Short-chain fatty acids (SCFAs) exhibit anticancer activity in cellular and animal models of colon cancer. Acetate, propionate, and butyrate are the three major SCFAs produced from dietary fiber by gut microbiota fermentation and have beneficial effects on human health. Most previous studies on the antitumor mechanisms of SCFAs have focused on specific metabolites or genes involved in antitumor pathways, such as reactive oxygen species (ROS) biosynthesis. In this study, we performed a systematic and unbiased analysis of the effects of acetate, propionate, and butyrate on ROS levels and metabolic and transcriptomic signatures at physiological concentrations in human colorectal adenocarcinoma cells. We observed significantly elevated levels of ROS in the treated cells. Furthermore, significantly regulated signatures were involved in overlapping pathways at metabolic and transcriptomic levels, including ROS response and metabolism, fatty acid transport and metabolism, glucose response and metabolism, mitochondrial transport and respiratory chain complex, one-carbon metabolism, amino acid transport and metabolism, and glutaminolysis, which are directly or indirectly linked to ROS production. Additionally, metabolic and transcriptomic regulation occurred in a SCFAs types-dependent manner, with an increasing degree from acetate to propionate and then to butyrate. This study provides a comprehensive analysis of how SCFAs induce ROS production and modulate metabolic and transcriptomic levels in colon cancer cells, which is vital for understanding the mechanisms of the effects of SCFAs on antitumor activity in colon cancer.

All-trans retinoic acid inhibits the malignant behaviors of hepatocarcinoma cells by regulating ferroptosis.

All-trans retinoic acid (ATRA) can reverse the malignant behaviors of hepatocellular carcinoma (HCC) cells, thereby exerting anti-HCC effect; however, the underlying mechanism is yet to be understood. This study aimed to demonstrate that ATRA is vital to ferroptosis in HCC. Ferroptosis-related genes exhibit different expression in patients with HCC compared to that in healthy individuals. A total of 20 amino acid products were detected in HepG2 cells, the expression level of 5 was decreased after ATRA treatment. ATRA improved the levels of lipid ROS, MDA, and NAPD+/NADPH, and reduced the mt-DNA copy number and changed the structure of mitochondria, in HepG2 and Hep3B cells. We found the expression of genes positively correlated with ferroptosis to increase and those negatively correlated to decrease with ATRA treatment. Inhibition of ferroptosis by Ferrostatin-1 reversed ATRA-inhibited proliferation of HCC cells, along with cell migration and invasion. GSH synthesis was blocked by ATRA, accompanied by decreased cystine content and increased glutamate content, and downregulation of the expression of GSH synthesis-related genes. Our findings suggested that ATRA inhibited the malignancy of HCC cells by improving ferroptosis, and that inhibition of GSH synthesis contributed to ATRA-induced ferroptosis.

Preparation, chemical structure, and immunostimulatory activity of a water-soluble heteropolysaccharide from Suillus granulatus fruiting bodies.

A water-soluble heteropolysaccharide (SGP2-1) was purified from Suillus granulatus fruiting bodies by anion-exchange chromatography and gel permeation chromatography. The structural characteristics were analyzed by high-performance gel permeation chromatography, high-performance liquid chromatography, Fourier transform infrared spectroscopy, gas chromatography-mass spectrometry, and nuclear magnetic resonance spectroscopy. The immunostimulatory activity was investigated using RAW 264.7 macrophages. Results showed that SGP2-1 with weight average molecular weight of 150.75 kDa was composed of mannose, glucose, and xylose. The backbone of SGP2-1 was mainly composed of â†’ 4)-α-Glcp-(1→, and the terminal group α-d-Glcp â†’ was linked to the main chain by O-6 position. SGP2-1 could significantly enhance pinocytic capacity, reactive oxygen species production, and cytokines secretion. SGP2-1 exerted immunomodulatory effects through interacting with toll-like receptor 2, and activating mitogen-activated protein kinase, phosphatidylinositol-3-kinase/protein kinase B, and nuclear factor-kappa B signaling pathways. These findings indicated that SGP2-1 could be explored as a potential immunomodulatory agent for application in functional foods.

Peroxidase from foxtail millet bran exerts anti-colorectal cancer activity via targeting cell-surface GRP78 to inactivate STAT3 pathway.

Molecular targeted therapy has become an emerging promising strategy in cancer treatment, and screening the agents targeting at cancer cell specific targets is very desirable for cancer treatment. Our previous study firstly found that a secretory peroxidase of class III derived from foxtail millet bran (FMBP) exhibited excellent targeting anti-colorectal cancer (CRC) activity in vivo and in vitro, whereas its underlying target remains unclear. The highlight of present study focuses on the finding that cell surface glucose-regulated protein 78 (csGRP78) abnormally located on CRC is positively correlated with the anti-CRC effects of FMBP, indicating it serves as a potential target of FMBP against CRC. Further, we demonstrated that the combination of FMBP with the nucleotide binding domain (NBD) of csGRP78 interfered with the downstream activation of signal transducer and activator of transcription 3 (STAT3) in CRC cells, thus promoting the intracellular accumulation of reactive oxygen species (ROS) and cell grown inhibition. These phenomena were further confirmed in nude mice tumor model. Collectively, our study highlights csGRP78 acts as an underlying target of FMBP against CRC, uncovering the clinical potential of FMBP as a targeted agent for CRC in the future.

Natural exosome-like nanovesicles from edible tea flowers suppress metastatic breast cancer via ROS generation and microbiota modulation.

Although several artificial nanotherapeutics have been approved for practical treatment of metastatic breast cancer, their inefficient therapeutic outcomes, serious adverse effects, and high cost of mass production remain crucial challenges. Herein, we developed an alternative strategy to specifically trigger apoptosis of breast tumors and inhibit their lung metastasis by using natural nanovehicles from tea flowers (TFENs). These nanovehicles had desirable particle sizes (131 nm), exosome-like morphology, and negative zeta potentials. Furthermore, TFENs were found to contain large amounts of polyphenols, flavonoids, functional proteins, and lipids. Cell experiments revealed that TFENs showed strong cytotoxicities against cancer cells due to the stimulation of reactive oxygen species (ROS) amplification. The increased intracellular ROS amounts could not only trigger mitochondrial damage, but also arrest cell cycle, resulting in the in vitro anti-proliferation, anti-migration, and anti-invasion activities against breast cancer cells. Further mice investigations demonstrated that TFENs after intravenous (i.v.) injection or oral administration could accumulate in breast tumors and lung metastatic sites, inhibit the growth and metastasis of breast cancer, and modulate gut microbiota. This study brings new insights to the green production of natural exosome-like nanoplatform for the inhibition of breast cancer and its lung metastasis via i.v. and oral routes.

Pure photosensitizer-driven nanoassembly with core-matched PEGylation for imaging-guided photodynamic therapy.

Pure drug-assembled nanomedicines (PDANs) are currently under intensive investigation as promising nanoplatforms for cancer therapy. However, poor colloidal stability and less tumor-homing ability remain critical unresolved problems that impede their clinical translation. Herein, we report a core-matched nanoassembly of pyropheophorbide a (PPa) for photodynamic therapy (PDT). Pure PPa molecules are found to self-assemble into nanoparticles (NPs), and an amphiphilic PEG polymer (PPa-PEG2K) is utilized to achieve core-matched PEGylating modification via the π‒π stacking effect and hydrophobic interaction between the PPa core and the PPa-PEG2K shell. Compared to PCL-PEG2K with similar molecular weight, PPa-PEG2K significantly increases the stability, prolongs the systemic circulation and improves the tumor-homing ability and ROS generation efficiency of PPa-nanoassembly. As a result, PPa/PPa-PEG2K NPs exert potent antitumor activity in a 4T1 breast tumor-bearing BALB/c mouse xenograft model. Together, such a core-matched nanoassembly of pure photosensitizer provides a new strategy for the development of imaging-guided theragnostic nanomedicines.

Localized disruption of redox homeostasis boosting ferroptosis of tumor by hydrogel delivery system.

Ferroptosis has received ever-increasing attention due to its unparalleled mechanism in eliminating resistant tumor cells. Nevertheless, the accumulation of toxic lipid peroxides (LPOs) at the tumor site is limited by the level of lipid oxidation. Herein, by leveraging versatile sodium alginate (ALG) hydrogel, a localized ferroptosis trigger consisting of gambogic acid (GA), 2,2'-azobis [2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH), and Ink (a photothermal agent), was constructed via simple intratumor injection. Upon 1064 â€‹nm laser irradiation, the stored AIPH rapidly decomposed into alkyl radicals (R•), which aggravated LPOs in tumor cells. Meanwhile, GA could inhibit heat shock protein 90 (HSP90) to reduce the heat resistance of tumor cells, and forcefully consume glutathione (GSH) to weaken the antioxidant capacity of cells. Systematic in vitro and in vivo experiments have demonstrated that synchronous consumption of GSH and increased reactive oxygen species (ROS) facilitated reduced expression of glutathione peroxidase 4 (GPX4), which further contributed to disruption of intracellular redox homeostasis and ultimately boosted ferroptosis. This all-in-one strategy has a highly effective tumor suppression effect by depleting and generating fatal active compounds at tumor sites, which would pave a new route for the controllable, accurate, and coordinated tumor treatments.

Cholesterol-associated lysosomal disorder triggers cell death of hematological malignancy: Dynamic analysis on cytotoxic effects of LW-218.

The integrity of lysosomes is of vital importance to survival of tumor cells. We demonstrated that LW-218, a synthetic flavonoid, induced rapid lysosomal enlargement accompanied with lysosomal membrane permeabilization in hematological malignancy. LW-218-induced lysosomal damage and lysosome-dependent cell death were mediated by cathepsin D, as the lysosomal damage and cell apoptosis could be suppressed by depletion of cathepsin D or lysosome alkalization agents, which can alter the activity of cathepsins. Lysophagy, was initiated for cell self-rescue after LW-218 treatment and correlated with calcium release and nuclei translocation of transcription factor EB. LW-218 treatment enhanced the expression of autophagy-related genes which could be inhibited by intracellular calcium chelator. Sustained exposure to LW-218 exhausted the lysosomal capacity so as to repress the normal autophagy. LW-218-induced enlargement and damage of lysosomes were triggered by abnormal cholesterol deposition on lysosome membrane which caused by interaction between LW-218 and NPC intracellular cholesterol transporter 1. Moreover, LW-218 inhibited the leukemia cell growth in vivo. Thus, the necessary impact of integral lysosomal function in cell rescue and death were illustrated.

Identification of ferroptosis as a novel mechanism for antitumor activity of natural product derivative a2 in gastric cancer.

Ferroptosis is a type of cell death accompanied by iron-dependent lipid peroxidation, thus stimulating ferroptosis may be a potential strategy for treating gastric cancer, therapeutic agents against which are urgently required. Jiyuan oridonin A (JDA) is a natural compound isolated from Jiyuan Rabdosia rubescens with anti-tumor activity, unclear anti-tumor mechanisms and limited water solubility hamper its clinical application. Here, we showed a2, a new JDA derivative, inhibited the growth of gastric cancer cells. Subsequently, we discovered for the first time that a2 induced ferroptosis. Importantly, compound a2 decreased GPX4 expression and overexpressing GPX4 antagonized the anti-proliferative activity of a2. Furthermore, we demonstrated that a2 caused ferrous iron accumulation through the autophagy pathway, prevention of which rescued a2 induced ferrous iron elevation and cell growth inhibition. Moreover, a2 exhibited more potent anti-cancer activity than 5-fluorouracil in gastric cancer cell line-derived xenograft mice models. Patient-derived tumor xenograft models from different patients displayed varied sensitivity to a2, and GPX4 downregulation indicated the sensitivity of tumors to a2. Finally, a2 exhibited well pharmacokinetic characteristics. Overall, our data suggest that inducing ferroptosis is the major mechanism mediating anti-tumor activity of a2, and a2 will hopefully serve as a promising compound for gastric cancer treatment.

Fucoxanthin-rich fraction from Sargassum fusiformis alleviates particulate matter-induced inflammation in vitro and in vivo.

Particulate matter (PM) contributes to air pollution and primarily originates from unregulated industrial emissions and seasonal natural dust emissions. Fucoxanthin (Fx) is a marine natural pigment from brown macroalgae that has been shown to have various beneficial effects on health. However, the effects of Fx on PM-induced toxicities in cells and animals have not been assessed. In this study, we investigated the anti-inflammatory potential of the Fx-rich fraction (FxRF) of Sargassum fusiformis against PM-mediated inflammatory responses. The FxRF composition was analyzed by rapid-resolution liquid chromatography mass spectrometry. Fx and other main pigments were identified. FxRF attenuated the production of inflammatory components, including prostaglandin E2 (PGE2), cyclooxygenase-2, interleukin (IL)-1ß, and IL-6 from PM-exposed HaCaT keratinocytes. PM exposure also reduced the levels of nitric oxide (NO), tumor necrosis factor-α, inducible nitric oxide synthase (iNOS), and PGE2 in PM-exposed RAW264.7 macrophages. Additionally, the culture medium from PM-exposed HaCaT cells induced upregulation of NO, iNOS, PGE2, and pro-inflammatory cytokines in RAW264.7 macrophages. FxRF also significantly decreased the expression levels of factors involved in inflammatory responses, such as NO, reactive oxygen species, and cell death, in PM-exposed zebrafish embryos. These results demonstrated the potential protective effects of FxRF against PM-induced inflammation both in vitro and in a zebrafish model.

Rhus semialata M. extract ameliorate para-phenylenediamine-induced toxicity in keratinocytes.

para-Phenylediamine (PPD), a major component of hair dyeing ingredients, can induce allergenic sensitization and exert mutagenic, tumorigenic and cytotoxic effect. In this study, we determined the cytotoxic effect of PPD on human keratinocytes and evaluated the protective effect of Rhus semialata M. extracts (RSE) on PPD induced cytotoxicity for the first time. We observed that RSE is a strong inhibitory agent against PPD-induced toxicity in human keratinocytes. The results indicated that RSE pretreatment significantly could suppress PPD induced cytotoxic effects, including decrease of cell viability, accumulation in subG1 phase of cells, and relocation of phosphatidylserine on keratinocytes. Also, we found that PPD caused cytotoxicity was associated with mitochondrial membrane potential loss and subsequent activation of caspase and PARP degradation. However, pretreatment of RSE showed preventive activities against PPD induced mitochondrial membrane potential loss and ROS production in keratinocytes. In conclusion, the results of present study suggest that RSE was able to protect the skin from several cytotoxic effects of PPD and could be a meaningful material in many industries using PPD.

Inhibitory effects of baicalein against herpes simplex virus type 1.

Herpes simplex virus type 1 (HSV-1) is a ubiquitous and widespread human pathogen, which gives rise to a range of diseases, including cold sores, corneal blindness, and encephalitis. Currently, the use of nucleoside analogs, such as acyclovir and penciclovir, in treating HSV-1 infection often presents limitation due to their side effects and low efficacy for drug-resistance strains. Therefore, new anti-herpetic drugs and strategies should be urgently developed. Here, we reported that baicalein, a naturally derived compound widely used in Asian countries, strongly inhibited HSV-1 replication in several models. Baicalein was effective against the replication of both HSV-1/F and HSV-1/Blue (an acyclovir-resistant strain) in vitro. In the ocular inoculation mice model, baicalein markedly reduced in vivo HSV-1/F replication, receded inflammatory storm and attenuated histological changes in the cornea. Consistently, baicalein was found to reduce the mortality of mice, viral loads both in nose and trigeminal ganglia in HSV-1 intranasal infection model. Moreover, an ex vivo HSV-1-EGFP infection model established in isolated murine epidermal sheets confirmed that baicalein suppressed HSV-1 replication. Further investigations unraveled that dual mechanisms, inactivating viral particles and inhibiting IκB kinase beta (IKK-ß) phosphorylation, were involved in the anti-HSV-1 effect of baicalein. Collectively, our findings identified baicalein as a promising therapy candidate against the infection of HSV-1, especially acyclovir-resistant strain.

Miltirone induces cell death in hepatocellular carcinoma cell through GSDME-dependent pyroptosis.

Pyroptosis is a form of programmed cell death, and recently described as a new molecular mechanism of chemotherapy drugs in the treatment of tumors. Miltirone, a derivative of phenanthrene-quinone isolated from the root of Salvia miltiorrhiza Bunge, has been shown to possess anti-cancer activities. Here, we found that miltirone inhibited the cell viability of either HepG2 or Hepa1-6 cells, and induced the proteolytic cleavage of gasdermin E (GSDME) in each hepatocellular carcinoma (HCC) cell line, with concomitant cleavage of caspase 3. Knocking out GSDME switched miltirone-induced cell death from pyroptosis to apoptosis. Additionally, the induction effects of miltirone on GSDME-dependent pyroptosis were attenuated by siRNA-mediated caspase three silencing and the specific caspase three inhibitor Z-DEVD-FMK, respectively. Miltirone effectively elicited intracellular accumulation of reactive oxygen species (ROS), and suppressed phosphorylation of mitogen-activated and extracellular signal-regulated kinase (MEK) and extracellular regulated protein kinases 1/2 (ERK1/2) for pyroptosis induction. Moreover, miltirone significantly inhibited tumor growth and induced pyroptosis in the Hepa1-6 mouse HCC syngeneic model. These results provide a new insight that miltirone is a potential therapeutic agent for the treatment of HCC via GSDME-dependent pyroptosis.

Inhibitory effects of Lentinus edodes mycelia polysaccharide on α-glucosidase, glycation activity and high glucose-induced cell damage.

At present, diabetes and diabetic complications have become one of the serious diseases affecting human health. In this study, the inhibitory effects of Lentinus edodes mycelia polysaccharide (LMP) on α-glucosidase activity, the formation of advanced glycation end products (AGEs) and high glucose-induced human umbilical vein endothelial cells (HUVECs) damage were explored. The interaction between LMP and α-glucosidase and the inhibition against AGEs formation were investigated with spectroscopic techniques. The results revealed that LMP had a reversible inhibition on α-glucosidase activity in a mixed-type manner. When the concentration of LMP was 2.7 mM, the inhibition rate was 34.38 %. LMP quenched the fluorescence of α-glucosidase through the static quenching and formed the LMP-α-glucosidase complex. At 310 K, the number of binding sites (n) and binding constant (Kb) were 1.01 and 3.71 × 104 L mol-1, respectively. In addition, LMP could inhibit the formation of AGEs. Compared with 40 mM glucose treatment group, treatment with 0.05 mM LMP for 48 h increased the cell viability from 70.17% to 91.14% and decreased ROS production from 3.33-fold to 1.21-fold. LMP inhibited high glucose-induced activation of MAPK signaling pathways. These findings may promote the application of LMP in the functional food industry.

Dietary fibres from guavira pomace, a co-product from fruit pulp industry: Characterization and cellular antioxidant activity.

Exotic fruits and their co-products may be valuable sources of antioxidant dietary fibres (DF) which are useful for food industry and human health. In this study, we aimed to characterize DF obtained from guavira fruit pomace and investigate its antioxidant potential employing TEAC assay as well as a cell model. The DF were chemically characterized as containing arabinan, highly-methoxylated homogalacturonan and arabinogalactan. The DF-containing fraction (CPW) presented ABTS free radical scavenger activity. MTT and DCFH-DA assay were performed to assess, respectively, changes in cell viability and the potential intracellular antioxidant activity against H2O2-induced oxidative stress in murine NIH 3T3 fibroblast. CPW exhibited no effects on cell viability, moreover, when administered 48 h prior the induction of H2O2 toxic effects, it protected the cells, significantly increasing the cell viability compared to control. This protection may be related to the observed reduction of reactive oxygen species levels. Thus, the pre-treatment of cells with guavira DF for 48 h remarkably induced a cytoprotection against pro-oxidant conditions, and may be a valuable functional compound recovered from an unexploited agroindutrial waste.

Targeting peptide-decorated biomimetic lipoproteins improve deep penetration and cancer cells accessibility in solid tumor.

The limited penetration of nanoparticles and their poor accessibility to cancer cell fractions in tumor remain essential challenges for effective anticancer therapy. Herein, we designed a targeting peptide-decorated biomimetic lipoprotein (termed as BL-RD) to enable their deep penetration and efficient accessibility to cancer cell fractions in a tumor, thereby improving the combinational chemo-photodynamic therapy of triple negative breast cancer. BL-RD was composed of phospholipids, apolipoprotein A1 mimetic peptide (PK22), targeting peptide-conjugated cytotoxic mertansine (RM) and photodynamic agents of DiIC18(5) (DiD). The counterpart biomimetic lipoprotein system without RM (termed as BL-D) was fabricated as control. Both BL-D and BL-RD were nanometer-sized particles with a mean diameter of less than 30 nm and could be efficiently internalized by cancer cells. After intravenous injection, they can be specifically accumulated at tumor sites. When comparing to the counterpart BL-D, BL-RD displayed superior capability to permeate across the tumor mass, extravasate from tumor vasculature to distant regions and efficiently access the cancer cell fractions in a solid tumor, thus producing noticeable depression of the tumor growth. Taken together, BL-RD can be a promising delivery nanoplatform with prominent tumor-penetrating and cancer cells-accessing capability for effective tumor therapy.

Prosthechea karwinskii, an orchid used as traditional medicine, exerts anti-inflammatory activity and inhibits ROS.

ETHNOPHARMACOLOGICAL RELEVANCE: Prosthechea karwinskii (Mart.) J.M.H. Shaw is a Mexican orchid used in traditional medicine by some indigenous communities to treat issues related to inflammation (cough, wounds, burns, and diabetes). Pharmacological research of this orchid could validate its therapeutic uses and demonstrate its potential for treating other health conditions of high prevalence in Mexico, including those associated with oxidative stress such as diabetes, cancer, atherosclerosis, and hypertension as well as inflammation. AIM OF THE STUDY: The leaf extract from P. karwinskii was examined to identify its compounds and elucidate its inhibitory effect on reactive oxygen species as well as its anti-inflammatory activity and gastroprotective effects in an animal model. MATERIALS AND METHODS: Compounds were identified via ultra-high-performance liquid chromatography coupled with electrospray ionization with quadrupole time of flight-mass spectrometry. Inhibition of reactive oxygen species was determined ex vivo in peripheral blood mononuclear cells with 2',7'-dichlorodihydrofluorescein diacetate. The anti-inflammatory activity was assessed using a carrageenan-induced paw edema model in Wistar rats; nitric oxide and tumor necrosis factor alpha levels were quantified. The gastroprotective effect was evaluated in Wistar rats with indomethacin-induced gastric injury. RESULTS: Nine compounds were identified in the P. karwinskii leaf extract. Most compounds, such as quinic acid, malic acid, neochlorogenic acid, chlorogenic acid, rutin, embelin, pinellic acid, and azelaic acid, were reported to exhibit antioxidant and/or anti-inflammatory activity. The extract was also found to inhibit reactive oxygen species in the ex vivo model. Unlike other anti-inflammatory drugs, the extract exerted a dual effect: anti-inflammatory activity and protection of the gastric mucosa. The results showed that the extract could significantly inhibit the release of nitric oxide without a dose-response relationship. CONCLUSION: P. karwinskii leaf extract inhibited reactive oxygen species and exerted an anti-inflammatory effect. Moreover, this extract did not induce gastric damage in the animals. The bioactivity of the species was found to support its use in traditional medicine. This orchid could be used to treat inflammatory diseases without causing the side effects associated with nonsteroidal anti-inflammatory drugs. It can also be employed to treat other pathological conditions associated with oxidative stress. The findings herein form the basis for the future discovery of natural products that may serve as safe alternative therapies for inflammatory disorders.