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To develop a transdermal delivery system for tetraphydrocurcumin nanoemulsion-gel (Thc@NE@gel), and to investigate its therapeutic efficacy and mechanism of action in atopic dermatitis (AD).
Thc@NE@gel was prepared using a high-energy emulsification method combined with a low-temperature swelling process. The formulation was characterized for particle size, zeta potential, drug loading, encapsulation efficiency, morphology and physicochemical properties. In vitro transdermal absorption experiments were conducted using a Franz diffusion cell. An AD mouse model was established, and successfully induced mice were randomly divided into animal control group, positive drug group (10mg·kg-1 dexamethasone gel), animal model group, Thc@NE group (Thc@NE 20 mg·kg-1) and animal Thc@NE@gel low-, medium- and high-dose experimental groups (10, 20, and 30 mg·kg-1 Thc@NE@gel), with 6 mice in each group. Body weights of mice in each group were measured and changes recorded; hematoxylin and eosin (HE) staining was performed to observe histopathological damage in skin tissue; enzyme-linked immunosorbent assay (ELISA) was used to detect serum inflammatory cytokine levels. Concurrently, an in vitro inflammatory model was established using human immortalized keratinocytes (HaCaT). Cells were divided into cell control group, cell model group (LPS 1 μg·mL-1), cell low- and high-dose Thc@NE@gel expreimental groups (10 and 30 μM Thc@NE@gel). Reactive oxygen species (ROS) were measured in each group using flow cytometry; serum inflammatory cytokine levels were detected by ELISA; Western blot analysis was performed to detect the expression of key proteins in the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway.
Thc@NE@gel was developed with a particle size of (195.30±5.20) nm, a zeta potential of (-24.51±1.45) mV, and a encapsulation efficiency of (72.70±0.67)%. The body weights of mice in the animal Thc@NE@gel low-, medium-, and high-dose treatment groups, the animal blank group, the animal model group, the Thc@NE group, and the positive control (dexamethasone) group on day 17 were (21.50±1.20), (22.30±1.15), (24.00±1.25), (26.20±1.30), (17.30±1.10), (18.20±1.15) and (17.50±1.05) g, respectively; immunoglobulin E(IgE) levels were (40.52±10.23), (32.84±9.65), (30.67±10.12), (21.23±3.45), (53.21±4.12), (56.45±5.89) and (64.32±12.14) ng·mL-1; IL-17 levels were (48.23±8.12), (25.43±4.67), (30.21±9.87), (23.45±5.12), (84.56±12.34), (54.12±5.67), and (47.89±6.78) pg·mL-1; IL-23 levels were (45.67±3.12), (44.23±2.98), (40.12±2.45), (25.34±7.12), (73.45±15.67), (55.23±6.78), and (24.56±1.89) pg·mL-1; when comparing the animal animal model group with the animal blank group, all of the above inflammatory markers showed statistically significant differences (all P<0.05). Compared with the animal model group, the IgE and IL-17 levels in the animal medium- and high-dose groups of Thc@NE@gel, as well as the IL-23 levels in all dose groups, showed statistically significant differences (all P<0.05); the IgE levels in the positive control group showed no statistically significant difference compared with the animal model group (P>0.05). Furthermore, the relative protein expression levels of cGAS in the low-dose and high-dose cell Thc@NE@gel experimental groups, the cell blank group, and the cell model group were 1.15±0.12, 0.82±0.08, 1.00±0, and 1.65±0.18, respectively; the relative protein expression levels of STING were 0.95±0.10, 0.60±0.06, 1.00±0.00, and 1.65±0.15, respectively. Compared with the animal blank group, all of the aforementioned indicators in the cell model group showed statistically significant differences (all P<0.001).
Thc@NE@gel enhances the anti-inflammatory effects of Thc, providing new insights for the development of skin delivery systems for natural active ingredients; furthermore, by inhibiting the cGAS-STING pathway, Thc@NE@gel improves atopic dermatitis, offering a new mechanistic perspective for its treatment.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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