Identification and molecular docking of tyrosinase inhibitory peptides from allophycocyanin in Spirulina platensis.

BACKGROUND: Tyrosinase, a copper-containing metalloenzyme with catalytic activity, is widely found in mammals. It is the key rate-limiting enzyme that catalyzes melanin synthesis. For humans, tyrosinase is beneficial to the darkening of eyes and hair. However, excessive deposition of melanin in the skin can lead to dull skin color and lead to pigmentation. Therefore, many skin-whitening compounds have been developed to decrease tyrosinase activity. This study aimed to identify a new tyrosinase inhibitory peptide through enzymatic hydrolysis, in vitro activity verification, molecular docking, and molecular dynamics (MD) simulation. RESULTS: A tripeptide Asp-Glu-Arg (DER) was identified, with a '-CDOCKER_Energy' value of 121.26 Kcal mol-1 . DER has effective tyrosinase inhibitory activity. Research shows that its half maximal inhibitory concentration value is 1.04 ± 0.01 mmol L-1 . In addition, DER binds to tyrosinase residues His85, His244, His259, and Asn260, which are key residues that drive the interaction between the peptide and tyrosinase. Finally, through MD simulation, the conformational changes and structural stability of the complexes were further explored to verify and supplement the results of molecular docking. CONCLUSION: This experiment shows that DER can effectively inhibit tyrosinase activity. His244, His259, His260, and Asn260 are the critical residues that drive the interaction between the peptide and tyrosinase, and hydrogen bonding is an important force. DER from Spirulina has the potential to develop functional products with tyrosinase inhibition. © 2024 Society of Chemical Industry.

Near-infrared light activated photosensitizer with specific imaging of lipid droplets enables two-photon excited photodynamic therapy.

Two-photon excited phototherapy has attracted considerable attention due to its advantages such as deeper penetration depth and higher spatial resolution. The lack of a high-performance photosensitizer with large two-photon absorption cross-sections and specific targeting ability makes the efficacy of phototherapy in the treatment of cancer unsatisfactory. Here, a new BODIPY-derived photosensitizer 6DBF2 is designed with two-photon photosensitization for two-photon excited photodynamic therapy in vivo. 6DBF2 possesses good two-photon absorption and efficient 1O2 generation upon near-infrared laser excitation. Excellent targeting specificities to lipid droplets of 6DBF2 without any encapsulation or modification at a low working concentration of 0.1 µM is in favor of efficient photodynamic therapy. In vitro cancer cell ablation and in vivo tumor ablation inside mice models upon two-photon irradiation in NIR demonstrate the outstanding therapeutic performance of 6DBF2 in two-photon excited photodynamic therapy. This work thus discusses a rare example of lipid droplets targeting two-photon excited photodynamic therapy for deep cancer tissue imaging and treatment under near-infrared light irradiation.

Self-Monitoring the Endo-Lysosomal Escape and Near-Infrared-Activated Mitophagy To Guide Synergistic Type-I Photodynamic and Photothermal Therapy.

Considering the multiple biological barriers before the entry of photosensitizers (PSs) into cytoplasm, it is of paramount importance to track PSs to elucidate their behaviors and distributions to guide the photodynamic therapy (PDT). Also, the developed PSs suffer from strong oxygen dependency. However, reports on such ideal theranostic platforms are rare. Herein, we developed a theranostic platform (CMTP-2) based on the coumarin-based D-π-A system, which, for the first time, can reveal the holistic intracellular delivery pathway and near-infrared (NIR)-activated mitophagy to guide synergistic type-I PDT and photothermal therapy. The dynamic endo-lysosomal escape of CMTP-2 was monitored, as well as its changeable distributions in endosomes, lysosomes, and mitochondria, demonstrating the preferential accumulation in mitochondria at the end. Upon NIR-I irradiation, CMTP-2 generated toxic radicals and heat, triggering the execution of mitophagy and apoptosis. In vivo experiments on mice indicated that CMTP-2 under 808 nm irradiation realized complete cancer ablation, showing great potential for advancements in synergistic phototherapy.

Defective transition metal hydroxide-based nanoagents with hypoxia relief for photothermal-enhanced photodynamic therapy.

Recently, phototherapy has attracted much attention due to its negligible invasiveness, insignificant toxicity and excellent applicability. The construction of a newly proposed nanosystem with synergistic photothermal and photodynamic tumor-eliminating properties requires a delicate structure design. In this work, a novel therapeutic nanoplatform (denoted as BCS-Ce6) based on defective cobalt hydroxide nanosheets was developed, which realized hypoxia-relieved photothermal-enhanced photodynamic therapy against cancer. Defective cobalt hydroxide exhibited high photothermal conversion efficacy at the near-infrared region (49.49% at 808 nm) as well as enhanced catalase-like activity to produce oxygen and greatly boost the singlet oxygen generation by a photosensitizer, Ce6, realizing efficacious dual-modal phototherapy. In vivo and in vitro experiments revealed that BCS-Ce6 can almost completely extinguish implanted tumors in a mouse model and present satisfactory biocompatibility during the treatment. This work sets a new angle of preparing photothermal agents and constructing comprehensive therapeutic nanosystems with the ability to modulate the hypoxic tumor microenvironment for efficient cancer therapy.

Liuwei Dihuang pill suppresses metastasis by regulating the wnt pathway and disrupting -catenin/T cell factor interactions in a murine model of triple-negative breast cancer.

OBJECTIVE: To investigate if the Liuwei Dihuang pill (LWDHP) can inhibit metastasis to the liver and lungs in mice bearing triple-negative breast cancer (TNBC), and the molecular mechanism underpinning this action. METHODS: Ninety-nine TNBC bearing-mice were distributed randomly to five groups: control (Con), paclitaxel (PTX), low-dose LWDHP (LLP, 2.3 g·kg－1·d－1), middle-dose LWDHP (MLP, 4.6 g·kg－1·d－1) and high-dose LWDHP (HLP, 9.2 g·kg－1·d－1). The LWDHP were administered (p.o.) to the agonal stage. The morphology of BC cells was observed by hematoxylin & eosin staining. Expression of axin-2, ß-catenin, T cell factor (TCF), cyclin- D1 and vascular endothelial growth factor (VEGF) was detected by western blotting or immunofluorescence. ß-catenin/TCF-1 interaction was measured using a co-immunoprecipitation assay. RESULTS: After LWDHP treatment, metastasis of BC cells to the lungs and liver was inhibited, expression of axin-2 was increased, expression of TCF-1, ß-catenin, cyclin-D1 and VEGF was decreased, and ß-catenin/TCF-1 interaction was disrupted. CONCLUSION: The LWDHP could inhibit metastasis of BC cells to the liver and lungs. The molecular mechanism underlying this action may be regulation of protein expression and ß-catenin/TCF-1 interactions in the Wnt pathway.

Short- and long-term antihypertensive effect of egg protein-derived peptide QIGLF.

BACKGROUND: The present study aimed to investigate the in vivo antihypertensive effect on spontaneously hypertensive rats (SHRs) induced by egg protein-derived peptide QIGLF, which has been previously characterized in vitro as a potent angiotensin-converting enzyme inhibitor. RESULTS: In vivo antihypertensive effect of QIGLF orally administered was evaluated by the tail-cuff method. The systolic blood pressure and the diastolic blood pressure of rats were measured 0, 5, 10, 15 and 20 h after administration every day. Subsequently, the effect of QIGLF on angiotensin-converting enzyme mRNA expression in the kidney of SHRs was evaluated by a polymerase chain reaction. Systolic blood pressure was found to be reduced markedly in the SHRs after a single oral administration. CONCLUSION: The results show that the effect of QIGLF (50 mg kg-1 body weight) was similar to that of captopril (10 mg kg-1 body weight) with respect to lowering systolic blood pressure in SHRs. Therefore, egg white protein-derived peptide QIGLF may be useful in the prevention or treatment of hypertension. © 2016 Society of Chemical Industry.

Comparison of anti-diabetic effects of polysaccharides from corn silk on normal and hyperglycemia rats.

Corn silk is well known and frequently used in traditional Chinese herbal medicines. Polysaccharides of corn silk (POCS), which were extracted by distilled water and precipitated by 80% ethanol solution, were evaluated for its anti-diabetic effect on streptozotocin (STZ)-induced diabetic rats. The results demonstrated that daily treatment with 100-500 mg/kg body weight of POCS on the diabetic rats could not only lead a significant decrease on the animal's blood glucose (BG) level, but also reduce the serum lipid level including total cholesterol (TC) and total triglyceride (TG) after determination. The oral glucose tolerance test (OGTT) was also performed to evaluate hypoglycemic effects. Through the measurements of measuring autonomic activity times and rolling stick times, the results also exhibited that the animals had been depressed by dimethyl-biguanide, but protected by the POCS. The POCS showed good antidepressant activity and lengthened remarkably the activity time during the autonomic activities test and exhibited a dose dependent activity.

Optimized extraction of polysaccharides from corn silk by pulsed electric field and response surface quadratic design.

BACKGROUND: Corn silk is a traditional Chinese herbal medicine, which has been widely used for treatment of some diseases. In this study the effects of pulsed electric field on the extraction of polysaccharides from corn silk were investigated. RESULTS: Polysaccharides in corn silk were extracted by pulsed electric field and optimized by response surface methodology (RSM), based on a Box-Behnken design (BBD). Three independent variables, including electric field intensity (kV cm(-1) ), ratio of liquid to raw material and pulse duration (µs), were investigated. The experimental data were fitted to a second-order polynomial equation and also profiled into the corresponding 3-D contour plots. Optimal extraction conditions were as follows: electric field intensity 30 kV cm(-1) , ratio of liquid to raw material 50, and pulse duration 6 µs. Under these condition, the experimental yield of extracted polysaccharides was 7.31% ± 0.15%, matching well with the predicted value. CONCLUSION: The results showed that a pulsed electric field could be applied to extract value-added products from foods and/or agricultural matrix.