Formulation and evaluation of a topical liposomal gel containing a combination of zedoary turmeric oil and tretinoin for psoriasis activity.

This study was to develop a combination of zedoary turmeric oil (ZTO) and tretinoin (TRE)-loaded liposomal gel as a topical drug delivery system. We used a combination of single-factor experiment and orthogonal experiment to systematically optimize encapsulation process of the compound liposomes. The optimized liposome vesicles were incorporated into Carbopol gel matrix and studied by continuous in vitro (skin penetration and retention) and in vivo (anti-psoriatic activity using mouse vaginal model and mouse tail model) experiments. The optimized liposomes had an entrapment efficiency (EE) of ZTO was (64.63 ± 1.00)%, EE of TRE was (90.33 ± 0.72)%, drug loading (DL) of ZTO was (9.09 ± 0.14)%, DL of TRE was (1.43 ± 0.02)%, particle size of 257.41 ± 7.58 nm, polydispersity index (PDI) of 0.10 ± 0.04 and zeta potential of -38.77 ± 0.81 mV. Transmission electron microscopy showed liposomes had a regular spherical surface. After 1-month storage at (4 ± 2)°C, the optimized liposome preparations maintained its stability. In vitro study indicated that liposome formulations could significantly prolong the penetration of drugs into the hair follicles of mice and keep more drugs in the skin compared with conventional gel formulations. In vivo study showed that liposomal gel was more effective than conventional gel in treating psoriasis and had a significant dose-dependent effect on psoriasis. In summary, liposomal gel is expected to be an ideal carrier for topical drug delivery systems of ZTO and TRE.

Iron chelation prevents nigrostriatal neurodegeneration in a chronic methamphetamine mice model.

Methamphetamine (METH) has been established to selectively target and impair dopaminergic neurons through multiple pathways. Ferroptosis is a unique form of non-apoptotic cell death driven by cellular iron accumulation-induced lipid peroxidation. Nonetheless, it remains unclear whether METH can induce ferroptosis. In the present study, we sought to assess alterations in iron levels after chronic METH exposure and reveal the modulatory role of iron on METH-induced pathologies. Importantly, we demonstrated that METH increased iron deposition in the nigrostriatal system, including the substantia nigra (SN) and caudate putamen (CPu). Moreover, decreases in GPx4 levels, increases in lipid peroxidation products, and pathological alterations were observed in the nigrostriatal system as a consequence of chronic METH exposure. The iron chelator deferiprone not only alleviated nigrostriatal iron deposition, dopaminergic cell death, and lipid peroxidation, but alsoattenuated the decreases in GPx4 induced by METH. These findings suggest an alleviation of ferroptosis in dopaminergic neurons. In addition, we found that the ferroptosis inhibitor liproxstatin-1 attenuated METH-induced dopaminergic degeneration in the nigrostriatal system. Our findings corroborated that METH might induce dopaminergic neurodegeneration through iron-dependent ferroptosis. Interestingly, reducing iron levels or inhibiting ferroptosis may alleviate METH-induced dopaminergic neurodegeneration.

Network Pharmacology-Based Prediction of the Active Compounds, Potential Targets, and Signaling Pathways Involved in Danshiliuhao Granule for Treatment of Liver Fibrosis.

This study aims to predict the active ingredients, potential targets, signaling pathways and investigate the "ingredient-target-pathway" mechanisms involved in the pharmacological action of Danshiliuhao Granule (DSLHG) on liver fibrosis. Pharmacodynamics studies on rats with liver fibrosis showed that DSLHG generated an obvious anti-liver fibrosis action. On this basis, we explored the possible mechanisms underlying its antifibrosis effect using network pharmacology approach. Information about compounds of herbs in DSLHG was collected from TCMSP public database and literature. Furthermore, the oral bioavailability (OB) and drug-likeness (DL) were screened according to ADME features. Compounds with OB≥30% and DL≥0.18 were selected as active ingredients. Then, the potential targets of the active compounds were predicted by pharmacophore mapping approach and mapped with the target genes of the specific disease. The compound-target network and Protein-Protein Interaction (PPI) network were built by Cytoscape software. The core targets were selected by degree values. Furthermore, GO biological process analysis and KEGG pathway enrichment analysis were carried out to investigate the possible mechanisms involved in the anti-hepatic fibrosis effect of DSLHG. The predicted results showed that there were 108 main active components in the DSLHG formula. Moreover, there were 192 potential targets regulated by DSLHG, of which 86 were related to liver fibrosis, including AKT1, EGFR, and IGF1R. Mechanistically, the anti-liver fibrosis effect of DSLHG was exerted by interfering with 47 signaling pathways, such as PI3K-Akt, FoxO signaling pathway, and Ras signaling pathway. Network analysis showed that DSLHG could generate the antifibrosis action by affecting multiple targets and multiple pathways, which reflects the multicomponent, multitarget, and multichannel characteristics of traditional Chinese medicine and provides novel basis to clarify the mechanisms of anti-liver fibrosis of DSLHG.

Preliminary study on the effect of brazilin on biofilms of Staphylococcus aureus.

Biofilms significantly enhance antibiotic resistance by inhibiting penetration of antibiotics and are shielded from the immune system via the formation of an extracellular polymeric matrix. Innovative and novel approaches are required for the inhibition of biofilm formation and treatment of biofilm-associated infectious diseases. In the current study, a biofilm model of Staphylococcus aureus was established in vitro to explore inhibitory effects of brazilin (BN) on biofilm formation and to evaluate damaging effects of BN in the presence and absence of vancomycin (VCM) on the biofilm. Antibiofilm-infection mechanisms of BN were observed. In these experiments, the clinical strain of S. aureus C-4-4 was isolated for biofilm formation. Crystal violet staining and fluorescence microscopy revealed that BN inhibited biofilm formation in vitro and the best effect was observed with two times the minimum inhibitory concentration of BN following 48 h incubation. Additionally, the results demonstrated that BN in combination with VCM enhanced the damage to biofilms, whereas VCM alone did not. The results of the reverse transcription-quantitative polymerase chain reaction analyses demonstrated that BN downregulated gene expression of intercellular adhesion (ica)A and upregulated icaR and the quorum-sensing (QS) system regulator accessory gene regulator A. In summary, BN inhibited S. aureus biofilm formation and destroyed biofilms, while simultaneously increasing permeability to VCM. BN was able to reduce production of the extracellular polymeric matrix and inhibited the QS system. These results support the use of BN as a novel drug and treatment strategy for S. aureus biofilm-associated infections.

[Effects of compound preparation of Cordyceps sinensis and Tripterygium hypoglaucum on survival time of pigskin after allogeneic transplantation].

OBJECTIVE: To investigate the effects of compound preparation of Cordyceps sinensis and Tripterygium hypoglaucum (CSTHC) on survival time of grafted pigskin after allogeneic transplantation and its mechanism. METHODS: The pigskin was treated with CSTHC solution before allogeneic transplantation, and CSTHC ointment was applied for external use on the grafted pigskin after skin transplantation. Cyclosporine A (CsA) and normal saline were served as control. The survival time, the appearance and the histomorphological changes of the grafted pigskin were observed. The histomorphological changes of testicles in pigs were also examined. The CD4 and CD8 expressions in the grafted pigskins were measured by immunohistochemical method. The white blood cell count in peripheral blood and the liver and renal functions were also examined. RESULTS: The survival time of the grafted pigskin in the CSTHC-treated group was (28.50+/-3.26)d, which was much longer as compared with (10.60+/-1.52)d in the untreated group (P<0.01). The survival time of the grafted pigskin in the CsA-treated group was (28.33+/-3.50)d, and there was no remarkable difference in the survival time of the grafted pigskin between the CsA-treated group and the CSTHC-treated group. The expressions of CD4 and CD8 were lower in the CSTHC-treated group than those in the untreated group on the 7th and 14th day after skin graft (P<0.05), while there was no significant difference in the indices between the CSTHC-treated group and the CsA-treated group. The WBC count was higher in the untreated group than that in the CSTHC-treated group or CsA-treated group on the 7th day after skin graft (P<0.05). CONCLUSION: CSTHC can prolong the survival time of allogeneic grafted pigskin. Its mechanism of inhibiting the immunological rejection may relate to decreasing the expressions of CD4(+) and CD8(+) in the grafted pigskin and reducing the local inflammatory reaction.