Ruthenium(II) complexes of curcumin and ß-diketone derivatives: effect of structural modifications on their cytotoxicity.

Ruthenium(II) complexes (Ru1-Ru3) with the general formula [Ru(O-O)(PPh3)2(bipy)]PF6, bearing two triphenylphosphine (PPh3), bipyridine (bipy) and a series of natural and synthetic ß-diketones (O,O) ligands were synthesized and characterized using various analytical techniques. The interaction between the complexes and calf thymus DNA (CT-DNA) was investigated and demonstrated a weak interaction. The cytotoxicity of the complexes was investigated against breast cancer cells (MDA-MB-231 and MCF-7), lung cancer cells (A549), cisplatin-resistant ovarian cancer cells (A2780cis), as well as non-tumour lung (MRC-5) and non-tumour breast (MCF-10A) cell lines. All complexes exhibited cytotoxic activity against all the cell lines studied, with half maximal inhibitory concentration (IC50) values ranging from 0.39 to 13 µM. Notably, the three complexes demonstrated selectivity against the A2780cis cell line, with IC50 ranging from 0.39 to 0.82 µM. Among them, Ru2 exhibited the highest cytotoxicity, with an IC50 value of 0.39 µM. Consequently, this new class of complexes shows good selectivity towards cisplatin-resistant ovarian cancer cells and it is promising for further investigation as anti-cancer agents.

Fabrication and Characterization of Electrospun Ocimum sanctum and Curcumin-Loaded Nanofiber Membrane for the Management of Periodontal Disease: An In Vitro Study.

Background Periodontal disease is a chronic inflammatory condition that gradually deteriorates the supportive tissues of teeth, eventually leading to tooth loss. Mechanical debridement stands as the gold standard method for treating periodontitis. However, antimicrobial therapy is recommended for optimal results when used alongside mechanical debridement. Numerous studies have investigated local drug delivery as an adjunct to mechanical debridement of affected tooth surfaces. Ocimum sanctum exhibits anti-inflammatory, antioxidant, and antimicrobial properties. Similarly, curcumin, as documented in the literature, demonstrates a broad spectrum of anti-inflammatory and antimicrobial effects. Electrospinning has demonstrated itself to be a highly effective method for fabricating drug-loaded fibers. Electrospun nanofibers containing Ocimum sanctum and curcumin are expected to exhibit greater efficacy due to their increased surface area, facilitating the dispersion of larger quantities of drugs, and their ability to control drug release when employed as a local drug delivery system. This study aims to fabricate and characterize the properties of nanofiber membranes loaded with Ocimum sanctum and curcumin using the electrospinning technique. Methods About 50 mg each of Ocimum sanctum and curcumin were blended with 15% polyvinyl alcohol and 2% chitosan polymer in a 4:1 ratio and left to stir overnight. A 10 mL syringe was filled with this solution, and an 18 G blunt-end needle charged at 15.9 kV was used for extrusion. Continuous fibers were collected onto a collector plate positioned 12 cm from the center of the needle tip, at a flow rate of 0.005 mL/min. The morphology of the fabricated membrane was assessed through scanning electron microscopy (SEM), the strength of the material was assessed through tensile strength analysis using INSTRON, an Electropuls E3000 Universal Testing Machine (INSTRON, Norwood, MA), and the drug release pattern was analyzed using Jasco V-730 UV-visible spectrophotometer (Jasco, Easton, MD). Results The morphology of this nanofiber showed a random distribution of fibers with no bead formation. The average diameter of the membrane was 383±102 nm, and the tensile strength of this material was 1.87 MPa. The drug release pattern showed an initial burst release of Ocimum sanctum, followed by a controlled release in subsequent hours. However, curcumin showed very little drug release because of its solubility. Conclusion In summary, the Ocimum sanctum and curcumin-loaded nanofibers exhibited robust tensile strength, a controlled drug release profile, and uniform drug distribution within the nanofiber membrane. Consequently, it can be concluded that curcumin nanofibers and electrospun Ocimum sanctum serve as valuable agents for local drug delivery in the treatment of periodontitis.

Dermal derived matrix hydrogel loaded with curcumin improved wound healing in a diabetic rat model.

There is a need in clinical practice for new wound healing techniques to address full thickness skin injuries, particularly in individuals with diabetes. Herein we investigated whether dermal derived matrix hydrogel (DMH) loaded with curcumin (Cur) could promote healing in diabetic rats. Sixty diabetic rats were randomly assigned into the non-treated group, DMH group, Cur group, and DMH+Cur group. According to the phases of wound healing, sampling was done on days 7, 14, and 21 for further assessments. Our results indicated that the wound contraction rate, new epidermal length and thickness, number of fibroblasts and vascular length, collagen deposition, and strength properties of the healed wounds were meaningfully increased in the treatment groups than in the non-treated group, and these changes were more obvious in the DMH+Cur ones. In addition, the expression of VEGF and IL-10 genes were meaningfully upregulated in all treatment groups compared to the non-treated group and were greater in the DMH+Cur group. This is while the number of neutrophils and expression levels of TNF-α and IL-1ß genes decreased more significantly in the DMH+Cur group compared to the other groups. In conclusion, it was found that using both DMH and curcumin has a greater impact on diabetic wound healing.

Sexual dysfunction in dichlorvos-exposed male Wistar rat is ameliorated by curcumin and associated with the upregulation of testosterone.

Dichlorvos is an organophosphate pesticide that is commonly used for agricultural and domestic control of pests and insects. Despite its usefulness, it exerts reproductive toxicity and induces male sexual dysfunction. On the other hand, curcumin has been reported to improve sexual dysfunction. However, till date, no study has reported the impact of curcumin on dichlorvos-induced sexual dysfunction. This study investigated the effect and associated mechanism of curcumin on dichlorvos-induced sexual dysfunction. Thirty-two male Wistar rats were randomized into four groups; the control (1 mL of olive oil), curcumin-treated (100 mg/kg), DDVP-treated (98.54 g/m3 of dichlorvos by inhalation), and DDVP + Curcumin-treated. Dichlorvos induced sexual dysfunction as depicted by reduced motivation to mate (8.38 ± 0.18 vs. 4.00 ± 0.33, P < 0.0001), prolonged latencies (46.63 ± 1.30 vs. 98.75 ± 1.32, P < 0.0001) and reduced frequencies of mount (14.88 ± 0.52 vs. 8.63 ± 0.38), intromission (9.38 ± 0.50 vs. 3.75 ± 0.31, P < 0.0001), and ejaculation (7.63 ± 0.38 vs. 1.50 ± 0.19, P < 0.0001). These findings were accompanied by suppression of hypothalamic-pituitary-testicular axis, evidenced by marked reductions in circulating FSH (60.00 ± 1.04 vs. 21.13 ± 0.52, P < 0.0001), LH (46.38 ± 1.38 vs. 19.00 ± 0.46, P < 0.0001), and testosterone (6.01 ± 0.50 vs. 0.74 ± 0.05, P < 0.0001). Nonetheless, the administration of curcumin in dichlorvos-exposed rats significantly attenuated dichlorvos-induced sexual dysfunction by improving the assessed indices of male sexual act. Also, curcumin significantly increased serum levels of FSH (21.13 ± 0.52 vs. 47.25 ± 0.10, P < 0.0001), LH (19.00 ± 0.46 vs. 43.00 ± 1.49), and testosterone (0.74 ± 0.05 vs. 3.98 ± 0.08, P < 0.0001). This study revealed that curcumin attenuated dichlorvos-induced sexual dysfunction by activating the hypothalamic-pituitary-testicular axis and upregulating circulating testosterone.

Development of UPLC-MS/MS method for studying the pharmacokinetic interactions of fuzuloparib with curcumin in rats.

Fuzuloparib is a novel orally bioactive poly-ADP-ribose polymerase inhibitor (PARPi), which was approved by the Chinese Regulatory Agency (CRA) in 2020 for the treatment of platinum-sensitive recurrent ovarian, fallopian tube, and primary peritoneal cancers. This study firstly presents a rapid and accurate ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for analyzing the levels of fuzuloparib and its major metabolite (SHR165202), and to investigate drug-drug interaction between fuzuloparib and curcumin in vitro and in vivo studies. After protein precipitation with acetonitrile, mobile phase consisted of acetonitrile and 0.1 % formic acid with a gradient elution was used to successfully separate fuzuloparib, SHR165202 and talazoparib (internal standard, IS). The results indicated that fuzuloparib and SHR165202 had good linearity over the calibration range of 2-50 ng/mL and 1-20 ng/mL, respectively. The precision, accuracy, stability, matrix effect, and extraction recovery required for methodological validation all complied with the requirements of the Bioanalytical Method Validation Guidelines. In vitro microsome incubation experiments, curcumin exhibited inhibitory effect on fuzuloparib in both rat liver microsomes (RLM) and human liver microsomes (HLM) with half-maximal inhibitory concentration (IC50) value of 10.54 µM and 47.64 µM, respectively, and the corresponding mechanism was non-competitive. Furthermore, the inhibitory mechanism of curcumin on fuzuloparib was validated through molecular docking. In pharmacokinetic experiments in rats, curcumin significantly altered the plasma exposure of fuzuloparib, resulting in significant increases in AUC(0-t) and Cmax of fuzuloparib and a significant decrease in CLz/F. Moreover, the metabolite SHR165202 showed significant increases in AUC(0-t), AUC(0-∞), Tmax and Cmax and a significant decrease in CLz/F. This further supports the notion that curcumin could inhibit the metabolism of fuzuloparib. Therefore, when co-administering fuzuloparib and curcumin in clinic, it is recommended to monitor plasma levels of fuzuloparib and pay close attention to adverse effects. If necessary, the dose of fuzuloparib needs to be reduced.

Unveiling the role of gut microbiota in curcumin metabolism using antibiotic-treated mice.

Curcumin might exert its therapeutic effects by interacting with gut microbiota. However, the role of gut microbiota in curcumin metabolism in vivo remains poorly understood. To address this, we used antibiotics to deplete gut microbiota and compared curcumin metabolism in control and antibiotic-treated mice. Using Q-TOF and triple quadrupole mass spectrometry, we identified and quantified curcumin metabolites, revealing distinct metabolic pathways in these two mice groups. The novel metabolites, hexahydro-dimethyl-curcumin and hexahydro-didemethyl-curcumin were exclusively derived from gut microbiota. Additionally, gut bacteria deconjugated curcumin metabolites back into their bioactive forms. Moreover, control mice exhibited significantly lower curcumin degradation, suggesting a protective role of gut microbiota against degradation. In conclusion, our results indicated that gut microbiota might enhance the effectiveness of curcumin by deconjugation, production of active metabolites, and protection against degradation in the large intestine. This study enhances our understanding of the interactions between curcumin and gut microbiota.

Curcumin inhibits growth of Porphyromonas gingivalis by arrest of bacterial dipeptidyl peptidase activity.

Background: Curcumin is a multi-functional polyphenol with anti-bacterial and anti-inflammatory effects and may have potential for treatment of periodontal diseases. The present study was conducted to examine the molecular basis of the anti-bacterial effect of curcumin against Porphyromonas gingivalis using metabolome analysis. Materials and Methods: P. gingivalis were incubated with 10 µg/mL curcumin, and then metabolites were analyzed with CE-TOF/MS. Expression levels of sigma factors were also evaluated using RT-PCR assays. The activities of dipeptidyl peptidases (DPPs) were assessed by examining the degradation reactions of MCA-labeled peptides. Results: The relative amounts of various glycogenic amino acids were significantly decreased when P. gingivalis was incubated with curcumin. Furthermore, the metabolites on the amino acid degradation pathway, including high-energy compounds such as ATP, various intermediate metabolites of RNA/DNA synthesis, nucleoside sugars and amino sugars were also decreased. Additionally, the expression levels of sigma-54 and sigma-70 were significantly decreased, and the same results as noted following nutrient starvation. Curcumin also significantly suppressed the activities of some DPPs, while the human DPP-4 inhibitors markedly inhibited the growth of P. gingivalis and activities of the DPPs. Conclusions: Curcumin suppresses the growth of P. gingivalis by inhibiting DPPs and also interferes with nucleic acid synthesis and central metabolic pathways, beginning with amino acid metabolism.

Enhancing the efficacy of antimicrobial photodynamic therapy through curcumin modifications.

Curcumin serves as a photosensitizer (PS) in the context of microbial inactivation when subjected to light exposure, to produce reactive oxygen species, which exhibit efficacy in eradicating microorganisms. This remarkable property underscores the growing potential of antimicrobial photodynamic therapy (aPDT) in the ongoing fight against bacterial infections. Considering this, we investigate the efficacy of various in vitro curcumin formulations within a PDT protocol designed to target Staphylococcus aureus. Specifically, we conduct a comparative analysis involving synthetic curcumin (Cur-Syn) and curcumin derivatives modified with chlorine (Cl), selenium (Se), and iodine (I) (Cur-Cl, Cur-Se, Cur-I). To assess the impact of aPDT, we subject S. aureus to incubation with curcumin, followed by irradiation at 450 nm with energy doses of 3.75, 7.5, and 15 J/cm2. Our investigation encompasses an evaluation of PS uptake and photobleaching across the various curcumin variants. Notably, all three modifications (Cur-Cl, Cur-Se, Cur-I) induce a significant reduction in bacterial viability, approximately achieving a 3-log reduction. Interestingly, the uptake kinetics of Cur-Syn and Cur-Se exhibit similarities, reaching saturation after 20 min. Our findings suggest that modifications to curcumin have a discernible impact on the photodynamic properties of the PS molecule.

Reduction-Responsive Polyprodrug Nanoplatform Based on Curcumin for Tumor-Targeted Therapy.

INTRODUCTION: Polymer prodrug nanoparticles have become an emerging drug delivery system in cancer therapy due to their high drug loading. However, their poor drug release and lack of tumor cell targeting limit their clinical application. OBJECTIVE: This study aimed to prepare targeted and reduction-reactive polyprodrug nanocarriers based on curcumin (CUR) for co-delivery of doxorubicin (DOX), labeled as DOX/HAPCS NPs, and to investigate their anticancer activity. METHODS: The polymer was synthesized and characterized by chemical method. The drug loading and drug release behavior of DOX and CUR in polymer nanoparticles were determined. Moreover, the antitumor effects of polymer nanoparticles were evaluated using an MTT experiment and tumor inhibition experiment, and the synergistic effect of co-delivered DOX and CUR was explored. RESULTS: The particle size of DOX/HAPCS NPs was 152.5nm, and the potential was about -26.74 mV. The drug-carrying capacity of DOX and CUR was about 7.56% and 34.75%, respectively, indicating high drug-carrying capacity and good stability. DOX and CUR released over 90% within 24 hours in the tumor environment. Compared with free DOX, DOX/HAPCS NPs demonstrated significantly enhanced cell and tumor inhibitory effects (P< 0.05) in vivo and in vitro and changed drug distribution to avoid toxic side effects on normal tissues. The combined index showed that DOX and CUR showed synergistic anticancer effects at a set ratio. CONCLUSION: The prepared reduction-responsive targeted polymer nanomedical DOX/HAPCS NPs exhibited a synergistic anti-cancer effect, with high drug loading capacity and the ability to release drugs in proportion, making it a promising polymer nanoparticle drug delivery system.

Comparative effects of the conventional, ultrasonic, and laser-activated irrigation on penetration depth of three photosensitizers in the root canal system.

OBJECTIVES: This study compared the effects of conventional, ultrasonic, and laser-activated irrigation (LAI) on penetration depth of three photosensitizers (PSs) in the root canal system. MATERIALS AND METHODS: In this in vitro, experimental study, 120 extracted anterior teeth were decoronated such that the remaining root length was standardized at 12 mm. After root canal instrumentation with the ProTaper rotary system and irrigation with 5.25% NaOCl, the roots were assigned to 12 groups for the application of toluidine blue (TB), curcumin, and phycocyanin PSs combined with the LAI using erbium laser with 0.4 mm and 0.6 mm tips, ultrasonic activation, and conventional irrigation. The specimens were sectioned apicocoronally, and the dye penetration depth was quantified in the coronal, middle, and apical thirds under a stereomicroscope at x20 magnification. Data were analyzed by the Kruskal-Wallis and Dunn test (alpha=0.05). RESULTS: The effects of irrigation technique, PS type, and their interaction on dye penetration depth were significant at the apical, middle, and coronal thirds (P<0.0001). TB + LAI with 0.4- and 0.6-mm laser tips showed the highest penetration depth while phycocyanin + LAI or conventional irrigation showed the lowest penetration depth at all areas. Dye penetration depth was the highest in the coronal, and the lowest in the apical third. CONCLUSION: The LAI technique with erbium laser (0.4- and 0.6-mm tips) enhanced the penetration depth of TB. The tested irrigation techniques had no significant efficacy for enhancement of the penetration depth of curcumin and phycocyanin.

Co-administration of either curcumin or resveratrol with cisplatin treatment decreases hepatotoxicity in rats via anti-inflammatory and oxidative stress-apoptotic pathways.

Background: Cisplatin (CIS) is a broad-spectrum anticancer drug, with cytotoxic effects on either malignant or normal cells. We aimed to evaluate the hepatotoxicity in rats caused by CIS and its amelioration by the co-administration of either curcumin or resveratrol. Materials and Methods: Forty adult male rats divided into four equal groups: (control group): rats were given a saline solution (0.9%) once intraperitoneally, daily for the next 28 days; (cisplatin group): rats were given a daily oral dose of saline solution (0.9%) for 28 days after receiving a single dose of cisplatin (3.3 mg/kg) intraperitoneally for three successive days; (CIS plus curcumin/resveratrol groups): rats received the same previous dose of cisplatin (3.3 mg/kg) daily for three successive days followed by oral administration of either curcumin/resveratrol solution at a dose of (20 mg/kg) or (10 mg/kg) consequently daily for 28 days. Different laboratory tests (ALT, AST, ALP, bilirubin, oxidative stress markers) and light microscopic investigations were done. Results: Administration of CIS resulted in hepatotoxicity in the form of increased liver enzymes, oxidative stress markers; degenerative and apoptotic changes, the co-administration of CIS with either curcumin or resveratrol improved hepatotoxicity through improved microscopic structural changes, reduction in liver enzymes activity, decreased oxidative stress markers, improved degenerative, and apoptotic changes in liver tissues. Conclusion: Co-administration of either curcumin or resveratrol with cisplatin treatment could ameliorate hepatotoxicity caused by cisplatin in rats via anti-inflammatory and oxidative stress-apoptotic pathways.

Protective Action of Curcumin and Alpha-lipoic Acid, Against Experimental Ultraviolet-A/B Induced Dermal-injury in Rats.

The objective of this study was to examine the therapeutic efficacy of curcumin (CUR) and α-lipoic acid (ALA) in mitigating UV-A and UV-B-induced damage (UVAB) in rat dorsal skin. This was achieved through the utilisation of immunohistochemical (TUNEL), biochemical and stereological techniques. The rats in the UVAB, UVAB + CUR, and UVAB + ALA groups were subjected to UVAB irradiation for a period of two hours per day over the course of one month. The UVAB + CUR and UVAB + ALA groups were administered 100 mg/kg/day of curcumin and 100 mg/kg/day of α-lipoic acid via gavage 30 min prior to UVAB irradiation. The CUR group was administered 100 mg/kg/day of curcumin via gavage, while the ALA group received the same dose of α-lipoic acid. A significant change in the volume ratio of the dorsal skin epidermis and dermis was observed in the stereological findings of the rats in the UVAB group. These changes exhibited a favourable progression as a consequence of the CUR and ALA applications. In the UVAB group, TOS and OSI were significantly elevated as a consequence of the rise in oxidative stress. Conversely, the treatment groups demonstrated a notable reduction in TOS and OSI levels. The study also revealed a substantial increase in the number of apoptotic cells within the UVAB group. However, the treatment groups exhibited a significant decline in apoptotic cells. In conclusion, the findings suggest that CUR and ALA possess a protective effect against UVAB-induced skin damage.

Non-isocyanate polyurethane-co-polyglycolic acid electrospun nanofiber membrane wound dressing with high biocompatibility, hemostasis, and prevention of chronic wound formation.

The prevention of chronic wound formation has already been a primary subject in wound management, particularly for deep wounds. The electrospun nanofiber membranes hold tremendous potential in the prevention of chronic wounds due to their micro/nano pore structures. Currently, many natural and synthetic materials have been utilized in the fabrication of nanofiber membranes. However, striking a balance between the structural stability and the biocompatibility remains challenging. It is necessary not only to ensure the long-term durability of nanofiber membranes but also to enhance their biocompatibility for alleviating patients' suffering. In this study, we reported a nanofiber membrane dressing with excellent biocompatibility and mechanical properties, which is potential for the treatment of deep wounds. The basal material chosen for the preparation of the nanofiber membrane was a co-polyester (NI-LPGD5) synthesized by non-isocyanate polyurethane (NIPU) and polyglycolic acid with a dihydroxy structure (LPGD-synthesized from glycolic acid and neopentyl glycol). Moreover, curcumin was also added as a bioactive substance to enhance the pro-healing effect of dressings. The physicochemical properties of the prepared nanofiber membranes were characterized through various physicochemical tools. Our results demonstrated that the NI-LPGD5 co-polymer can be electrospun into smooth fibers. Meanwhile, curcumin-loaded nanofiber membranes (Cur/NI-LPGD5) also exhibited a favorable microscopic morphology. The fabricated membranes exhibited suitable mechanical properties, outstanding hygroscopic-swelling rate and water vapor transmittance. Besides, in vitro cell culturing, the cells on the NI-LPGD5 membrane maintained their maximum viability. The potential of in vivo wound healing was further demonstrated through animal experiments. The experimental results showed that the nanofiber membranes effectively prevented chronic wounds from forming and promoted granulation tissue growth without replacing the dressing throughout the healing process. We also found that these nanofiber membranes could effectively promote the expression of related biomarkers to accelerate wound healing, particularly the Cur/NI-LPGD5 membrane. In conclusion, the fabricated membranes possess suitable physicochemical properties and promising bioactivity. As a result, it effectively prevented the formation of chronic wounds and demonstrated significant potential in reducing the frequency of dressing changes.

Water soluble curcumin with alkyl sulfonate moiety: Synthesis, and anticancer efficacy.

Curcumin is classified as a chemotherapeutic medication because of its potential against numerous cancer cell lines and ability to inhibit cancer cell proliferation. Despite these findings, curcumin has yet to be commercialized as a drug due to its low water solubility, low absorption, and restricted bioavailability. As a result, there is a demand for water-soluble curcumin with improved solubility, bioavailability, and thus bioactivity. In this study we report the synthesis and the anticancer activities of water-soluble curcumins derivatives with alkyl sulfonate moiety. The target water-soluble curcumin with alkyl sulfonate moieties was created utilizing a straightforward technique that involved reacting curcumin with various sultones. The cytotoxic (24 h) and cytostatic (72 h) anticancer effect on breast carcinoma (MCF-7), liver carcinoma (HepG2), skin melanoma (B16-F110), colon human cancer and HeLa cervical carcinoma cell lines viability % via MTT assay were determined for the prepared derivatives. Results showed that curcumin-derived compounds have a pronounced cytostatic anticancer effect rather than cytotoxic one in relation to the compound type, cancer cell line type, and examined concentration compared to curcumin. The curcumin sulfonates outperformed curcumin activity against the tested cancer cells and showed to be powerful anticancer candidate drugs as supported by the theoretical calculations. This is evident by their high capacity to form H-bonding during docking with the amino acid side chains and the Vina docking score.

Magnetic curcumin-copper graphene oxide as facile and recyclable heterogeneous nanocatalyst for preparation of polyhydroquinolines and sulfoxides.

In this research project, a versatile procedure has been designed for the preparation of supported copper@curcumin on magnetic graphene oxide nanoparticles (GO@Fe3O4@Cur-Cu). The structure of prepared nanocatalyst was characterized by several techniques including; Fourier transform infrared, powder X-ray diffraction, thermal gravimetric analysis, energy dispersive X-ray analysis, inductively coupled plasma optical emission spectroscopy, vibrating sample magnetometer, transmission electron microscopy, and scanning electron microscopy analyses. The catalytic properties of GO@Fe3O4@Cur-Cu were examined for the efficient synthesis of polyhydroquinolines as well as the preparation of sulfoxides through selective oxidation of sulfides in the presence of hydrogen peroxide.

Effects of chain length and saturation of triacylglycerols on the characteristics and gastrointestinal digestion fates of curcumin-loaded triacylglycerol nanoparticles.

This study assessed the effects of fatty acid length and saturation on the physicochemical, thermal, and gastrointestinal digestive characteristics of curcumin-loaded homo-triacylglycerol nanoparticles (C-NPs). All C-NPs had good colloidal stability and efficiently entrapped curcumin, regardless of their length and saturation. Tricaprylin NPs, with shorter chains, had a smaller size and emulsifier surface load. Curcumin was released faster from low-melting C-NPs (tricaprylin and triolein) than those with high-melting-point (trimyristin, tripalmitin, and tristearin); however, both were negligible without lipolysis. None of the C-NPs underwent significant aggregation, coalescence, or breakdown during digestion before the small intestine. Notably, longer and more saturated chains resulted in a slower initial rate and lower degree of lipolysis in the small intestine. However, greater bioaccessibility of curcumin was observed only with longer chains (tricaprylin, 70.72%; trimyristin, 78.05%; tripalmitin, 85.09%; tristearin, 89.65%; triolein, 89.71%). These findings could be valuable for the development of rational curcumin formulations for functional foods.

The effects of berberine and curcumin on cardiac, lipid profile and fibrosis markers in cyclophosphamide-induced cardiac damage: The role of the TRPM2 channel.

Cyclophosphamide (CYP) is widely used to treat various types of cancer. In addition to the therapeutic properties of this drug, unfortunately, its side effects are still not fully understood. This study investigated the protective effect of curcumin (CURC) and berberine (BER) on CYP-induced cardiac damage. Thirty-six male rats were equally divided into the control, dimethyl sulfoxide (DMSO), CYP, CYP + CURC, CYP + BER and CYP + BER + CURC groups. Troponin-I, Creatine kinase-myocardial band (CK-MB), total cholesterol, triglyceride levels in serum samples, and reactive oxygen species (ROS), poly(ADP-ribose) polymerase-1 (PARP-1), and transient receptor potential melastatin 2 (TRPM2) channel levels in heart tissue were measured using an enzyme-linked immunoassay (ELISA) kit. In addition, histopathological examination and immunohistochemical investigation of the TRPM2 channel, fibroblast specific protein-1 (FSP1), transforming growth factor-beta- 1 (TGF-ß1) and α-smooth muscle actin (α-SMA) expressions were determined in heart tissue. The CYP group's troponin-I, total cholesterol, triglyceride, CK-MB, ROS, PARP-1 and TRPM2 channel levels were higher than in the other groups in the ELISA measurements (p < 0.05). In contrast, these parameters in the group treated with CURC and BER together with CYP were lower than in the CYP group (p < 0.05). Additionally, CUR and BER reduced CYP-induced pathological damage, TRPM2, FSP1, TGF-ß1 and α-SMA expressions. The data showed that CYP administration can cause cardiac damage by increasing the TRPM2 channel, TGF-ß1, FSP1 and α-SMA expression levels. Therefore, we concluded that CURC and BER administration following CYP application may be used as therapeutic agents to prevent CYP-induced cardiac damage.

Cytokine Storm in COVID-19: Insight into Pathological Mechanisms and Therapeutic Benefits of Chinese Herbal Medicines.

Cytokine storm (CS) is the main driver of SARS-CoV-2-induced acute respiratory distress syndrome (ARDS) in severe coronavirus disease-19 (COVID-19). The pathological mechanisms of CS are quite complex and involve multiple critical molecular targets that turn self-limited and mild COVID-19 into a severe and life-threatening concern. At present, vaccines are strongly recommended as safe and effective treatments for preventing serious illness or death from COVID-19. However, effective treatment options are still lacking for people who are at the most risk or hospitalized with severe disease. Chinese herbal medicines have been shown to improve the clinical outcomes of mild to severe COVID-19 as an adjunct therapy, particular preventing the development of mild to severe ARDS. This review illustrates in detail the pathogenesis of CS-involved ARDS and its associated key molecular targets, cytokines and signalling pathways. The therapeutic targets were identified particularly in relation to the turning points of the development of COVID-19, from mild symptoms to severe ARDS. Preclinical and clinical studies were reviewed for the effects of Chinese herbal medicines together with conventional therapies in reducing ARDS symptoms and addressing critical therapeutic targets associated with CS. Multiple herbal formulations, herbal extracts and single bioactive phytochemicals with or without conventional therapies demonstrated strong anti-CS effects through multiple mechanisms. However, evidence from larger, well-designed clinical trials is lacking and their detailed mechanisms of action are yet to be well elucidated. More research is warranted to further evaluate the therapeutic value of Chinese herbal medicine for CS in COVID-19-induced ARDS.

Repeated dose, 28-day oral toxicity study of curcumin, anthocyanins, and sodium nitrite in Wistar rats.

OBJECTIVE: The goal of the present study was to examine the repeated dose 28-day oral toxicity of curcumin, anthocyanins, and sodium nitrite in Wistar rats. METHODS: For this purpose, forty-eight male Wistar rats were randomly divided into 8 groups (n = 6 each), encompassing untreated controls and experimental groups treated with curcumin, anthocyanins, and sodium nitrite. Three rats from each group were sacrificed by cervical dislocation under di-ethyl ether anesthesia after 2 and 4 weeks of therapy, respectively. Blood samples were collected for serum chemistry. All of the animals' livers, hearts, and kidneys were removed and sent for histopathological examination. RESULTS: After two weeks of inquiry, certain groups displayed higher hematological values, while others had lower values compared to the control group. AST, CK, and LDH enzyme activity were higher in groups 2-8, but urea concentrations were higher in groups 6 and 8. After four weeks, the Hb, MCH, and MCHC values in group 4 were greater, as were the WBC levels in groups 4 and 6, whereas other groups had lower MCV and WBC values. The weekly body weight gain was insignificantly different between treatment groups. Throughout the experiment, none of the animals perished. Male rats' liver, kidney, and heart underwent histopathological changes after ingesting curcumin, sodium nitrite, and anthocyanin. CONCLUSION: Based on the findings, rats were more detrimental when curcumin, sodium nitrite, and anthocyanin were ingested together than when they were consumed individually, as evidenced by histopathological abnormalities in the liver, kidneys, and heart.

Curcumin-Rich Diet Mitigates Non-Alcoholic Fatty Liver Disease (NAFLD) by Attenuating Fat Accumulation and Improving Insulin Sensitivity in Aged Female Mice under Nutritional Stress.

BACKGROUND: The high incidence of metabolic syndrome in the elderly poses a significant challenge to the healthcare system, emphasizing the need for interventions tailored to geriatric patients. Given the limited focus on females in previous studies, this research aimed to evaluate the effects of dietary curcumin on obesity and NAFLD outcomes in naturally aged (18-month-old) female mice. METHODS: Female C57BL/6 mice aged 18 months were fed a normal chow diet (NCD) and a HFHSD, with or without curcumin (0.4% w/w), for an 8-week period. Parameters included food intake, body weight, insulin tolerance test (ITT), glucose tolerance test (GTT), percentage fat mass, hepatic triglyceride, and cholesterol levels, and a histological examination for NAFLD detection, qPCR, and immunoblotting analyses were performed. RESULTS: The cumulative body weight gain after 8 weeks in the aged female mice supplemented with curcumin and fed an HFHSD was significantly lower (10.84 ± 1.09 g) compared to those fed a HFHSD alone (15.28 ± 1.26 g). Curcumin supplementation also resulted in reduced total body fat (HFHSD group 50.83 ± 1.71% vs. HFHSD+CUR 41.46 ± 3.21%), decreased epidydimal fat mass (HFHSD: 3.79 ± 0.29 g vs. HFHSD+CUR: 2.66 ± 0.30 g), and repaired adipogenic signaling in the white adipose tissue. Furthermore, curcumin lowered triglyceride and cholesterol deposition in the liver, preventing hepatic steatosis and improving hepatic insulin sensitivity. CONCLUSIONS: Curcumin demonstrates the ability to ameliorate the deleterious effects of HFHSD in aged female mice by reducing body fat composition, modulating adipogenic signaling in the white adipose tissue, and improving insulin homeostasis and non-alcoholic fatty deposition in the liver.