Jinhong Hu

Curcumin Inhibits Imiquimod-Induced Psoriasis-Like Inflammation by Inhibiting IL-1beta and IL-6 Production in Mice

Curcumin, a selective phosphorylase kinase inhibitor, is a naturally occurring phytochemical present in turmeric. Curcumin has been confirmed to have anti-inflammatory properties in addition to the ability to decrease the expression of pro-inflammatory cytokines in keratinocytes. The interleukin-23 (IL-23)/IL-17A cytokine axis plays a critical role in the pathogenesis of psoriasis. Here, we report that topical use of a curcumin gel formulation strongly inhibited imiquimod (IMQ)-induced psoriasis-like inflammation, the development of which was based on the IL-23/IL-17A axis. IMQ-induced epidermal hyperplasia and inflammation in BALB/c mouse ear was significantly inhibited following curcumin treatment. Real-time PCR showed that mRNA levels of IL-17A, IL-17F, IL-22, IL-1β, IL-6 and TNF-α cytokines were decreased significantly by curcumin in ear skin, an effect similar to that of clobetasol. In addition, we found that curcumin may enhance the proliferation of epidermis γδ T cells but inhibit dermal γδ T cell proliferation. We inferred that curcumin was capable of impacting the IL-23/IL-17A axis by inhibiting IL-1β/IL-6 and then indirectly down-regulating IL-17A/IL-22 production. In conclusion, curcumin can relieve the IMQ-induced psoriasis-like inflammation in a mouse model, similar to the effects of clobetasol. Therefore, we have every reason to expect that curcumin will be used in the treatment of psoriasis in the future.

Substance P receptor expression in human skin keratinocytes and fibroblasts

Background  There is increasing evidence that neuropeptides, especially substance P (SP), may be involved in the pathogenesis of cutaneous allergic inflammation (CAI).

Strong cellular and humoral immune responses induced by transcutaneous immunization with HBsAg DNA-cationic deformable liposome complex.

Abstract:  Transcutaneous immunization presents a major challenge on account of poor permeability of antigens through the skin barrier. To overcome this limitation, the deformable liposome could be a better method for transcutaneous delivery of these antigens. In this study, hepatitis B surface antigen (HBsAg) plasmid DNA–cationic complex deformable liposome was utilized as a mode for enhanced immunity against the antigen. Deformable liposome was prepared by conventional rotary evaporation method and characterized for various parameters such as vesicles shape and surface morphology, size and size distribution, entrapment efficiency, elasticity and stability. The immune stimulating activity was studied by measuring serum anti‐HBsAg titre and cytokines level (interleukin‐4 and interferon‐γ) following topical application of liposome in BALB/c mice and results were compared with deformable liposome encapsulated DNA applied topically as well as naked DNA and pure recombinant HBsAg, administered intramuscularly. It was observed that deformable liposome elicited a comparable serum antibody titre and endogenous cytokines levels compared to other vaccinations. The study signifies the potential of deformable liposome as DNA vaccine carriers for effective transcutaneous immunization.

Mannose 6‐phosphate‐modified bovine serum albumin nanoparticles for controlled and targeted delivery of sodium ferulate for treatment of hepatic fibrosis

Objectives The aim was to prepare neoglycoprotein‐based nanoparticles for targeted drug delivery to hepatic stellate cells, and to evaluate their characteristics in vitro and in vivo.

Curcumin induces apoptosis in tumor necrosis factor-alpha-treated HaCaT cells

Psoriasis is a benign, chronic skin disease characterized by keratinocyte hyperproliferation and abnormal differentiation. Curcumin, a selective phosphorylase kinase inhibitor, is a natural phytochemical present in turmeric. Curcumin has been confirmed to have anti-inflammatory properties as well as the ability to inhibit proliferation and decrease the expression of pro-inflammatory cytokines in psoriatic keratinocytes. However, the pro-apoptotic effect of curcumin in keratinocytes remains unclear. In the present study, we investigated the effect of curcumin on apoptosis induction in TNF-α-treated HaCaT cells. These results show that curcumin exhibited a significant pro-apoptotic effect on HaCaT cells only in the presence of TNF-α and/or TRAIL. The pro-apoptotic effect of curcumin resulted from the increased expression of TRAIL-R1/R2 and the decreased expression of anti-apoptotic proteins. Our results indicate that both curcumin and TNF-α up-regulated the expression of TRAIL-R1/R2. In addition, the expression of anti-apoptotic proteins (IAP1, IAP2, Bcl-X(L)) was up-regulated by TNF-α but suppressed by curcumin in HaCaT cells. Because these proteins are regulated by NF-κB, we examined the role of curcumin in NF-κB activation. As expected, curcumin inhibited TNF-α-induced activation of NF-κB, including NF-κB-P65. Curcumin also inhibited the TNF-α-induced production of IL-6/IL-8 in HaCaT cells. These results imply that curcumin-induced apoptosis of HaCaT cells only occurs when TNF-α or/and TRAIL are present. Therefore, we believe that curcumin is able to reverse the anti-apoptotic function of TNF-α in HaCaT cells and thus expect curcumin to be successful in the treatment of psoriasis.

Ginsenoside Rb1 and paeoniflorin inhibit transient receptor potential vanilloid-1-activated IL-8 and PGE2 production in a human keratinocyte cell line HaCaT

Ginsenoside Rb1 (GRb1) and paeoniflorin (PF) are active substances of Chinese traditional herbs and have been commonly used to treat skin inflammation diseases, but little is known about the mechanisms involved. In the present study, the effects of GRb1 and PF on the production of inflammatory mediators and the possible mechanisms of transient receptor potential vanilloid-1 (TRPV1) in these mediators induction were explored. It has been shown that GRb1 and PF inhibited the productions of IL-8 and PGE₂ induced by capsaicin (CAP) in HaCaT cells and HEK 293T-TRPV1 cells (which were transgenic and overexpressed TRPV1) but had no effect on HEK 293T mock cells (p<0.05). Besides, CAP was able to induce calcium influx and nuclear factor kappa B(NF-κB) transcriptional activity in HaCaT cells and HEK 293T-TRPV1 cells, but had no effect on HEK 293T mock cells. Furthermore, GRb1 inhibited CAP-induced calcium influx and NF-κB transcriptional activity in both HaCaT cells and HEK 293T-TRPV1 cells. However, PF decreased CAP-induced calcium influx and NF-κB transcriptional activity only in HaCaT cells. This would suggest that GRb1 inhibits CAP-induced calcium influx and NF-κB activity through TRPV1 signal, while calcium influx and NF-κB activity might not be involved in the inhibitory effect of PF on TRPV1 signal. Furthermore, the inhibitory rates of GRb1 and PF on IL-8 and PGE₂ production were higher than those caused by capsazepine, an antagonist of TRPV1, suggesting that GRb1 and PF have great potential in clinical treatment of skin diseases.

A modified LC‐MS/MS method for determination of tetramethylpyrazine in microdialysis samples and calibration of home‐made linear probes

Tetramethylpyrazine (TMP) is one of the most important active ingredients of a Chinese herb Ligusticum wallichii Franchat, which is widely used for the treatment of cardiovascular diseases. Several factors may affect TMP exposure after topical administration, resulting in large variability and demanding further elucidation of drug distribution. This paper describes a new efficient reliable LC-MS/MS assay for the determination of TMP in dermal microdialysate, where TMP was separated on an Agilent C(18) column (3.5 µm, 100 mm × 2.1 mm i.d.) using a mixture of methanol, water and acetic acid (50:50:0.6, v/v/v) at a flow-rate of 0.3 mL/min. The retention time was 1.89 min for TMP and 1.17 min for the internal standard (caffeine). Histological analysis confirmed an inflammatory response to the microdialysis probes and the presence of a collagen capsule. The membrane extraction efficiency (percentage delivered to the tissue space) for TMP was not altered through the implant lifetime. The validation and sample analysis results showed that the method is precise, accurate and well suited to support dermal microdialysis experiments.

A novel spray-dried nanoparticles-in-microparticles system for formulating scopolamine hydrobromide into orally disintegrating tablets

Scopolamine hydrobromide (SH)-loaded microparticles were prepared from a colloidal fluid containing ionotropic-gelated chitosan nanoparticles using a spray-drying method. The spray-dried microparticles were then formulated into orally disintegrating tablets (ODTs) using a wet granulation tablet formation process. A drug entrapment efficiency of about 90% (w/w) and loading capacity of 20% (w/w) were achieved for the microparticles, which ranged from 2 μm to 8 μm in diameter. Results of disintegration tests showed that the formulated ODTs could be completely dissolved within 45 seconds. Drug dissolution profiles suggested that SH is released more slowly from tablets made using the microencapsulation process compared with tablets containing SH that is free or in the form of nanoparticles. The time it took for 90% of the drug to be released increased significantly from 3 minutes for conventional ODTs to 90 minutes for ODTs with crosslinked microparticles. Compared with ODTs made with noncrosslinked microparticles, it was thus possible to achieve an even lower drug release rate using tablets with appropriate chitosan crosslinking. Results obtained indicate that the development of new ODTs designed with crosslinked microparticles might be a rational way to overcome the unwanted taste of conventional ODTs and the side effects related to SH’s intrinsic characteristics.

Development of a novel HPLC-MS/MS method for the determination of aconitine and its application to in vitro and rat microdialysis samples.

A sensitive and selective LC-MS/MS method was developed and validated for the determination of aconitine in microdialysate and rat plasma. Extraction of plasma sample was conducted by use of 1% trichloracetic acid and acetonitrile solution with 10 ng/mL internal standard (propafenone) spiked. Microdialysates were analyzed without sample purification. After sample preparation, 2 microL were injected and separated with an isocratic mobile phase consisting of acetonitrile:0.1% formic acid (60:40, v/v) at a flow rate of 0.3 mL/min. The Agilent G6410A triple quadrupole LC/MS system was operated under the multiple-reaction monitoring mode (MRM) using the electrospray ionization technique in positive mode. Overall, the assay exhibited good precision and accuracy. The diffusion properties of aconitine investigated in in vitro microdialysis experiments revealed unfavourable concentration dependence avertable by keeping a constant pH 5.77 using isotonic phosphate buffer solution as perfusate. The mean relative recoveries were 48.23% [coefficient of variation (CV 4.47%)] and 55.38% (CV 2.89%) for retrodialysis and recovery experiments, respectively. The in vivo recovery of aconitine was 34.48% (CV 3.05%) and was stable over the 6 h study period. Following characterization of aconitine both in vitro and in vivo microdialysis, the developed setting is suitable for application in pharmacokinetics and pharmacodynamics studies.

A comparison of the effects of topical treatment of calcipotriol, camptothecin, clobetasol and tazarotene on an imiquimod-induced psoriasis-like mouse model

Abstract The interleukin-23/interleukin 17A (IL-23/IL-17A) cytokine axis plays a critical role in the pathogenesis of psoriasis. In this study, we report the effects of topical calcipotriol, camptothecin, clobetasol and tazarotene on the treatment of imiquimod (IMQ)-induced psoriasis-like inflammation, the development of which is dependent on the IL-23/IL-17A axis. IMQ-induced epidermal hyperplasia and inflammation in the BALB/c mouse ear were significantly inhibited following clobetasol treatment but not calcipotriol, camptothecin or tazarotene treatments. Real-time polymerase chain reaction showed that the mRNA levels of IL-17A, IL-17F, IL-22, IL-1β, IL-6 and TNF-α in ear skin were significantly decreased by clobetasol. In addition, we observed that calcipotriol, camptothecin and tazarotene failed to show any inhibitory effects on the IL-23/IL-17A/IL-22 axis. We also found that clobetasol treatment inhibited the proliferation of γδ T cells and C-C chemokine receptor type 6 (CCR6) expression induced by IMQ. Calcipotriol, camptothecin and tazarotene not only failed to inhibit this proliferation but also enhanced retinoic acid-related orphan receptor γ (RORγ) expression in IMQ-induced psoriasis-like inflammation. In conclusion, we suggest that clobetasol induces the relief of IMQ-induced psoriasis-like inflammation in a mouse model but that calcipotriol, camptothecin and tazarotene cannot. Therefore, we suggest that more in-depth studies on pharmacological effects of tazarotene, camptothecin and calcipotriol should be carried out.