Liquiritin Carbomer Gel Cold Paste Promotes Healing of Solar Dermatitis in Mice 甘草苷聚卡波姆凝胶冷敷贴促进小鼠太阳皮炎的愈合
Yanfang Huang , Sijia , Jinghua Pan , Congjing Song , Weiqiang Chen and Yun Zhang Yanfang Huang ，Sijia ，Jinghua Pan ，Congjing Song ，Weiqiang Chen 和 Yun Zhang 1 School of Nursing, Guangdong Pharmaceutical University, Guangzhou 510006, China 广东药科大学护理学院，中国广州 5100062 School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China 广东药科大学药学院，中国广州 5100063 School of Basic Medical Sciences, Guangdong Pharmaceutical University, Guangzhou 510006, China 广东药科大学基础医学院，中国广州 510006* Correspondence: wqc@gdpu.edu.cn (W.C.); zhangyun@gdpu.edu.cn (Y.Z.) * 通讯：wqc@gdpu.edu.cn（W.C.）; zhangyun@gdpu.edu.cn（Y.Z.）+ These authors contributed equally to this work. 这些作者对这项工作做出了相等的贡献。
Citation: Huang, Y.; Li, S.; Pan, J.; Song, C.; Chen, W.; Zhang, Y. Liquiritin Carbomer Gel Cold Paste Promotes Healing of Solar Dermatitis in Mice. Int. J. Mol. Sci. 2024, 25, 3767. https://doi.org/10.3390/ijms25073767 引用：Huang，Y.；李，S.；潘，J.；宋，C.；陈，W.；张，Y.。甘草素卡波姆凝胶冷膏促进小鼠太阳皮炎愈合。国际分子科学杂志。2024 年，25 卷，3767 页。https://doi.org/10.3390/ijms25073767
Academic Editor: Christopher Jackson 学术编辑：克里斯托弗·杰克逊
Ultraviolet radiation (UVR) has various effects on human cells and tissues, which can lead to a variety of skin diseases and cause inconvenience to people's lives. Among them, solar dermatitis is one of the important risk factors for malignant melanoma, so prevention and treatment of solar dermatitis is very necessary. Additionally, liquiritin (LQ) has anti-inflammatory effects. In this study, we aimed to evaluate the anti-inflammatory and pro-wound healing effects of liquiritin carbomer gel cold paste (LQ-CG-CP) in vitro and in vivo. The results of MTT experiments showed no cytotoxicity of LQ at concentrations of and below and cell damage at UVB irradiation doses above . Moreover, LQ can promote cell migration. ELISA results also showed that LQ inhibited the elevation of the inflammatory factors tumor necrosis factor- (TNF- ), interleukin (IL-1 ), and interleukin-6 (IL-6) after UVB irradiation. In the mouse model of solar dermatitis, LQ-CG-CP showed the best therapeutic efficacy for wound healing and relief of itching compared to MEIBAO moist burn moisturizer (MEBO). What is more, the results of skin histopathological examination show that LQ-CG-CP promotes re-epithelialization, shrinks wounds, and promotes collagen production, thus promoting wound healing. Simultaneously, LQ-CG-CP reduced TNF- , IL-1 , and IL-6 expression. In addition, LQ-CG-CP was not observed to cause histopathological changes and blood biochemical abnormalities in mice. Overall, LQ-CG-CP has great potential for the treatment of solar dermatitis. 紫外线辐射（UVR）对人体细胞和组织有各种影响，可能导致多种皮肤疾病，并给人们的生活带来不便。其中，太阳性皮炎是恶性黑色素瘤的重要危险因素之一，因此预防和治疗太阳性皮炎非常必要。此外，甘草素（LQ）具有抗炎作用。在本研究中，我们旨在评估离体和体内甘草素羟丙基甲基纤维素凝胶冷贴（LQ-CG-CP）的抗炎和促伤口愈合效果。MTT 实验结果显示，LQ 在 及以下浓度下无细胞毒性，并且在 UVB 照射剂量超过 时造成细胞损伤。此外，LQ 可以促进细胞迁移。ELISA 结果还显示，在 UVB 照射后，LQ 抑制了炎症因子肿瘤坏死因子- （TNF- ）、白细胞介素 （IL-1 ）和白细胞介素-6（IL-6）的升高。在太阳性皮炎小鼠模型中，与 MEIBAO 湿烧伤保湿剂（MEBO）相比，LQ-CG-CP 对于伤口愈合和缓解瘙痒效果最好。 此外，皮肤组织病理学检查结果显示，LQ-CG-CP 促进了重新上皮化，收缩伤口，并促进了胶原蛋白的产生，从而促进了伤口愈合。同时，LQ-CG-CP 降低了 TNF-7，IL-1 和 IL-6 的表达。此外，在小鼠中未观察到 LQ-CG-CP 引起的组织病理学变化和血液生化异常。总的来说，LQ-CG-CP 在太阳性皮炎治疗方面具有巨大潜力。
Keywords: solar dermatitis; liquiritin carbomer gel cold paste; anti-inflammatory; wound healing 关键词：太阳皮炎；甘草苷卡波姆明胶冷敷膏；抗炎；伤口愈合
1. Introduction 1. 介绍
Nowadays, UVR has become one of the most important factors affecting people's lives due to its various effects on human skin tissue. Specifically, solar dermatitis, also known as sunburn, is an inflammation of the skin caused by exposure to excessive UVR in a sun-exposed environment, which usually leads to the appearance of erythematous pimples and blisters in sun-exposed areas, and self-consciousness of burning, itching, and pain [1]. The shoulders, neck, head, and face are the most common areas of sunburn, followed by the hands or arms and back [2]. The symptoms of solar dermatitis can bring inconvenience to patients' lives. A study analyzing data from a national sample of U.S. hospital emergency department visits in 2013 estimated 33,826 sunburn-related visits and an estimated USD 11.2 million in costs associated with emergency department visits [3]. A history of solar dermatitis is an important risk factor for malignant melanoma [4]. Therefore, the prevention and treatment of solar dermatitis is essential. 如今，紫外线辐射已成为影响人们生活的最重要因素之一，因为它对人体皮肤组织有各种影响。具体而言，太阳性皮炎，又称晒伤，是皮肤由于在阳光照射环境中暴露于过量紫外线辐射而引起的炎症，通常会导致暴露于阳光下的区域出现红斑丘疹和水疱，并伴有烧灼感、瘙痒和疼痛的自觉[1]。肩部、颈部、头部和面部是最常见的晒伤部位，其次是手部或臂部和背部[2]。太阳性皮炎的症状会给患者的生活带来不便。一项分析 2013 年美国全国样本医院急诊科就诊数据的研究估计有 33,826 次与晒伤相关的就诊，急诊科就诊相关成本估计为 1,120 万美元[3]。太阳性皮炎的病史是恶性黑素瘤的一个重要危险因素[4]。因此，预防和治疗太阳性皮炎至关重要。
UVR is categorized into three types based on their wavelengths: UVA (315-400 nm), UVB (280-315 nm), and UVC (100-280 nm); the atmosphere filters out most of the UVB and all of the UVC, so that the UVA and a portion of the UVB that reaches the Earth can cause damage to the human skin [5]. However, both act differently on the skin and only UVB induces characteristic epidermal sunburn damage [6]. UVB can induce an 紫外线根据其波长分为三种类型：UVA（315-400 纳米），UVB（280-315 纳米）和 UVC（100-280 纳米）; 大气层会过滤掉大部分 UVB 和所有 UVC，使得到达地球的 UVA 和部分 UVB 可以对人体皮肤造成损害[5]。然而，它们在皮肤上的作用不同，只有 UVB 引起特征性的表皮日晒损伤[6]。UVB 能够诱导
inflammatory response through several mechanisms . In addition, UV can directly activate keratinocytes and other cells to release inflammatory mediators such as TNF- , IL-1 , and IL-6 [9]. It has been shown that naringenin can inhibit skin edema induced by UVB irradiation, and also inhibit UVB irradiation-induced MMP-9 activity and the production of inflammatory factors to prevent UVB irradiation damage to mouse skin [10]. Verbenacea extract also had a protective effect on UVB-irradiated mice, inhibiting UVBinduced inflammatory responses as well as oxidative stress [11]. 炎症反应会通过几种机制 。此外，紫外线可以直接激活角质细胞和其他细胞释放炎症介质，如 TNF- ，IL-1 和 IL-6 [9]。已经证明柚皮素可以抑制 UVB 照射引起的皮肤水肿，并抑制 UVB 照射诱导的 MMP-9 活性和炎症因子的产生，以预防 UVB 照射对小鼠皮肤的损伤[10]。马鞭草提取物也对 UVB 照射的小鼠具有保护作用，抑制 UVB 诱导的炎症反应和氧化应激[11]。
In recent years, the role of licorice flavonoids has attracted the attention of some researchers, and their potential medicinal value and application areas have been continuously studied, and their newly developed products have better application prospects [12,13]. LQ is a licorice flavonoid compound extracted from licorice [14]. Its anti-inflammatory effects have been demonstrated in studies of diseases such as rheumatoid arthritis and lipopolysaccharide-induced acute lung injury . 近年来，甘草黄酮的作用引起了一些研究者的注意，其潜在药用价值和应用领域得到了持续研究，并且其新开发的产品具有更好的应用前景【12,13】。LQ 是从甘草中提取的甘草黄酮化合物【14】。研究表明，其具有抗炎作用，可用于类风湿性关节炎和脂多糖诱导的急性肺损伤等疾病的研究 。
Currently, the main research focus is on the protective and preventive effects of solar dermatitis, while this paper focuses on the therapeutic perspective. The carbomer gel selected in this study can prolong the retention time of the drug on the skin surface, improve the efficiency of drug use, and, on this basis, when combined with a cold compress paste, can soothe the burning, itching, and other discomforts caused by solar dermatitis. Therefore, this study proposed to study the therapeutic effect of LQ-CG-CP in promoting wound healing of solar dermatitis in mice and explore the mechanism of its treatment of solar dermatitis, to provide a certain research basis for the subsequent development of the cold paste of solar dermatitis therapeutic gel, which has a certain clinical application prospect. 目前，主要的研究重点是太阳皮炎的保护和预防效果，而本文则侧重于治疗角度。本研究选择的卡波姆凝胶可以延长药物在皮肤表面的停留时间，提高药物使用效率，在此基础上，与冷敷膏结合时，可以缓解太阳皮炎引起的灼烧、瘙痒和其他不适感。因此，本研究提出了研究 LQ-CG-CP 促进小鼠太阳皮炎伤口愈合的治疗效果，并探索其治疗太阳皮炎的机制，为后续太阳皮炎治疗凝胶冷敷膏的开发提供一定的研究基础，具有一定的临床应用前景。
2. Results 2. 结果
2.1. Effect of LQ and UVB on Cell Proliferation Viability 2.1. LQ 和 UVB 对细胞增殖活力的影响
To confirm the concentration of LQ used and the UVB modeling dose, the MTT assay was used to detect the effects of LQ and UVB on HaCaT and JB6 cells. As shown in Figure 1A,B, the viability of HaCaT and JB6 cells was significantly decreased at concentrations of LQ of or more, indicating that high concentrations of LQ were significantly toxic to the cells . Therefore, of LQ was used as the highest concentration for subsequent experiments. The survival rates of and JB6 cells were significantly decreased when UVB was at a dose of or above (Figure 1C,D). Compared with the blank control group, the cell survival rate in the dose group was higher than that in the 70 and dose groups, although it decreased; so, the dose of UVB was the optimal dose for the cell model. 为了确认所使用的 LQ 浓度和 UVB 模拟剂量，使用 MTT 测定法检测 LQ 和 UVB 对 HaCaT 和 JB6 细胞的影响。如图 1A、B 所示，HaCaT 和 JB6 细胞的存活率在 LQ 浓度为 或更高时显著降低，表明高浓度的 LQ 对细胞有明显毒性 。因此，将 LQ 的 用作后续实验的最高浓度。当 UVB 剂量为 或以上时， 和 JB6 细胞的存活率显著降低 （图 1C、D）。与空白对照组相比， 剂量组的细胞存活率高于 70 和 剂量组，尽管有所下降；因此，UVB 的 剂量是细胞模型的最佳剂量。
2.2. Effect of LQ on Cell Migration Capacity and UVB on Cell Secretion of Inflammatory Factors 2.2. LQ 对细胞迁移能力和 UVB 对细胞分泌炎症因子的影响
To assess whether LQ could promote cell migration, the cell scratch assay was used to detect the effects of different concentrations of on the migration rate of and JB6 cells. As shown in Figure 2A-D, LQ significantly increased HaCaT and JB6 cell scratch wound migration width . It is thus clear that LQ promotes and JB6 cell migration. 评估 LQ 是否能促进细胞迁移，使用细胞划痕实验检测不同浓度的 对 和 JB6 细胞迁移速率的影响。如图 2A-D 所示，LQ 显著增加了 HaCaT 和 JB6 细胞划痕伤口迁移宽度 。因此清楚地表明 LQ 促进了 和 JB6 细胞迁移。
To determine the effect of UVB on cell secretion of inflammatory factors, the ELISA assay was used to detect the effects of different UVB irradiation doses on the expression levels of cellular inflammatory factors. As shown in Figure 2E-J, the higher the UVB modeling dose, the higher the levels of TNF- , IL-1 , and IL-6. 为了确定 UVB 对细胞分泌炎症因子的影响，使用 ELISA 检测了不同 UVB 照射剂量对细胞炎症因子表达水平的影响。如图 2E-J 所示，UVB 建模剂量越高，TNF-α、IL-1β和 IL-6 水平越高。
2.3. Effect of LQ on Cell Secretion of Inflammatory Factors after UVB Irradiation 2.3. LQ 对 UVB 照射后细胞分泌炎症因子的影响
To determine whether LQ could inhibit the elevation of inflammatory factors in and JB6 cells induced by UVB irradiation, ELISA experiments were used to detect the effects of different LQ concentrations on the expression levels of inflammatory factors in and JB6 cells after UVB irradiation. As shown in Figure 3, the UVB irradiation dose significantly increased the expression levels of the inflammatory factors TNF- , IL-1 , and IL-6 in HaCaT and JB6 cells compared with the Control group ). In HaCaT cells, 确定 LQ 是否能抑制 UVB 照射诱导的 和 JB6 细胞中炎症因子的升高，ELISA 实验用于检测不同 LQ 浓度对 UVB 照射后 和 JB6 细胞中炎症因子表达水平的影响。如图 3 所示，与对照组相比（ ）， HaCaT 和 JB6 细胞中的 UVB 照射剂量显著增加了炎症因子 TNF- ，IL-1 和 IL-6 的表达水平。在 HaCaT 细胞中，
the administration of and LQ interventions significantly decreased the levels of TNF- , IL-1 , and IL-6 and alleviated the inflammatory response in a dose-dependent manner (Figure 3A-C). In JB6 cells, the administration of and LQ interventions significantly decreased the level of TNF- (Figure 3D); the administration of LQ interventions significantly decreased the level of IL-1 ) (Figure 3E); and the administration of LQ interventions failed to significantly decrease the level of IL-6, but it also followed an increase in dose and showed a decreasing trend ) (Figure 3F). 和 LQ 干预的管理显著降低了 TNF- ，IL-1 和 IL-6 的水平，并以剂量依赖的方式缓解了炎症反应（图 3A-C）。在 JB6 细胞中， 和 LQ 干预的管理显著降低了 TNF- 的水平（图 3D）； LQ 干预的管理显著降低了 IL-1 的水平（图 3E）；LQ 干预的管理未能显著降低 IL-6 的水平，但随着剂量的增加也呈现出下降的趋势 （图 3F）。
A
C
B
D
Figure 1. Effect of LQ and UVB on cell viability. (A) Effect of LQ on HaCaT cell viability; (B) Effect of LQ on JB6 cell viability; (C) Effect of UVB on HaCaT cell viability; and (D) Effect of UVB on JB6 cell viability. (ns ). 图 1. LQ 和 UVB 对细胞存活率的影响。(A) LQ 对 HaCaT 细胞存活率的影响；(B) LQ 对 JB6 细胞存活率的影响；(C) UVB 对 HaCaT 细胞存活率的影响；以及(D) UVB 对 JB6 细胞存活率的影响。(ns )。
2.4. The Promoting Effect of LQ on Skin Wound Healing and Its Ability to Alleviate Itching Symptoms in Mice 2.4. LQ 对小鼠皮肤伤口愈合的促进作用及其缓解瘙痒症状的能力
As shown in Figure 4A, which shows the process of skin wound changes in each group, the Control group is the normal skin of mice. Compared with the UVB group, the wound size was significantly smaller in the LQ-CG-CP group and the LQ-CG-CP group, which could also be found to be more effective than the application of CP and LQ-CG alone. In addition, the effect of the positive drug MEBO was not as significant as that of LQ-CG-CP. As shown in Figure 4B, after 7 days of treatment, the average wound healing rates of mice in the UVB group, CP group, LQ-CG group, LQ-CG-CP group, 1% LQ-CG-CP group, 2% LQ-CG-CP group, and MEBO group were , , and . Compared with the UVB group, the wound healing rates of mice in the CP, LQ-CG, LQ-CG-CP, LQ-CG-CP, LQ-CG-CP, and MEBO groups were significantly increased , with the most significant healing effect in the LQ-CG-CP and LQ-CG-CP groups. What is more, mice with solar dermatitis develop itching symptoms, and the severity of itchy skin symptoms in mice was visually evaluated by observing the number of scratches. As shown in Figure 4C, compared with the UVB group, the itching number of mice in the CP group decreased slightly, while the itching behaviors of mice in the LQ-CG group, the LQ-CG-CP group, the LQ-CG-CP group, the LQ-CG-CP group, and the MEBO group could be 如图 4A 图 4A 所示，展示了每组皮肤伤口变化的过程，对照组为小鼠正常皮肤。与 UVB 组相比，0 LQ-CG-CP 组和 1 LQ-CG-CP 组的伤口大小显著较小，这也比单独应用 CP 和 2 LQ-CG 更有效。此外，正性药物 MEBO 的效果并不如 LQ-CG-CP 显著。如图 4B 所示，在治疗 7 天后，UVB 组、CP 组、3 LQ-CG 组、4 LQ-CG-CP 组、1% LQ-CG-CP 组、2% LQ-CG-CP 组和 MEBO 组小鼠的平均伤口愈合率分别为 5、6 和 7。与 UVB 组相比，CP 组、8 LQ-CG 组、9 LQ-CG-CP 组、10 LQ-CG-CP 组、11 LQ-CG-CP 组和 MEBO 组小鼠的伤口愈合率显著增加，其中 ，在 14 LQ-CG-CP 组中愈合效果最为显著。此外，太阳性皮炎小鼠出现瘙痒症状，通过观察抓挠次数对小鼠的瘙痒皮肤症状 LQ-CG-CP 组具有最显著的愈合效果。此外，太阳皮炎小鼠会出现瘙痒症状，通过观察划痕数量对小鼠瘙痒皮肤症状的严重程度进行视觉评估。如图 4C 所示，与 UVB 组相比，CP 组小鼠的瘙痒次数略有减少，而 15 LQ-CG 组、16 LQ-CG-CP 组、17 LQ-CG-CP 组、18 LQ-CG-CP 组和 MEBO 组小鼠的瘙痒行为可能会稍有
significantly reduced ( , with the greatest decrease in the number of scratches of mice in the LQ-CG-CP group ( ), indicating the best effect. 显著减少（ ，老鼠在 LQ-CG-CP 组中划痕数量的减少最大（ ），表明效果最佳。
Figure 2. Effects of LQ and UVB on HaCaT and JB6 cells. (A) The change process of HaCaT cell scratch; (B) The scratch wound closure rate of HaCaT cells; (C) The change process of JB6 cell scratch; (D) The scratch wound closure rate of JB6 cells; (E-G) UVB-induced expression levels of inflammatory factors TNF- , IL-1 , and IL-6 in HaCaT cells; and (H-J) UVB-induced expression levels of inflammatory factors TNF- , IL-1 , and IL-6 in JB6 cells. (ns , , magnifications, ). 图 2. LQ 和 UVB 对 HaCaT 和 JB6 细胞的影响。 (A) HaCaT 细胞划痕的变化过程；(B) HaCaT 细胞划痕愈合速率；(C) JB6 细胞划痕的变化过程；(D) JB6 细胞划痕愈合速率；(E-G) HaCaT 细胞中 UVB 诱导的炎症因子 TNF- ，IL-1 和 IL-6 的表达水平；(H-J) JB6 细胞中 UVB 诱导的炎症因子 TNF- ，IL-1 和 IL-6 的表达水平。 (ns ， ，放大倍数， )。
2.5. Staining Results of Wound Skin Tissues 2.5. 伤口皮肤组织的染色结果
To study the process of LQ-CG-CP in promoting wound healing, mouse skin tissues were taken for and Masson staining to assess the rate of wound repair in mouse skin tissues after 7 days of administration. 研究 LQ-CG-CP 在促进伤口愈合过程中的作用，取得了小鼠皮肤组织用于 和 Masson 染色，以评估给药后小鼠皮肤组织在 7 天后的伤口修复速率。
The HE staining results are shown in Figure 5A. Some areas in the UVB model group were not completely healed, did not possess complete epidermis, and still had inflammatory cell infiltration. There was a significant difference in epidermal thickness in the UVB, CP, LQ-CG, LQ-CG-CP, LQ-CG-CP, and MEBO groups compared to the Control HE 染色结果如图 5A 所示。在 UVB 模型组中，一些区域并未完全愈合，未具有完整的表皮，仍然存在炎性细胞浸润。与对照组相比，UVB、CP、 LQ-CG、 LQ-CG-CP、 LQ-CG-CP 和 MEBO 组的表皮厚度存在显著差异。
group ( ). Compared with the UVB group, the epidermal thickness of the CP, LQCG, LQ-CG-CP, LQ-CG-CP, 2% LQ-CG-CP, and MEBO groups was significantly reduced (Figure 5B). In contrast, LQ-CG-CP had formed a complete epidermis, which was close to the skin histological structure of the blank control group. The epidermis of the MEBO group was thickened, the epidermis was still not completely healed, and the stratum corneum was disorganized. 组（ ）。与 UVB 组相比，CP， LQCG， LQ-CG-CP， LQ-CG-CP，2% LQ-CG-CP 和 MEBO 组的表皮厚度显著减少 （图 5B）。相反， LQ-CG-CP 形成了完整的表皮，接近空白对照组的皮肤组织结构。 MEBO 组的表皮变厚，表皮仍未完全愈合，角质层无序。
A
B
C
Figure 3. Effect of LQ on the expression levels of inflammatory factors in UVB-induced and JB6 cells. (A-C) The levels of TNF- , IL-1 , and IL-6 in HaCaT cells; and (D-F) The levels of TNF- , IL-1 , and IL-6 in JB6 cells. ( ; +: Positive, - : negative). 图 3。LQ 对 UVB 诱导的 HaCaT 和 JB6 细胞中炎症因子表达水平的影响。（A-C）HaCaT 细胞中 TNF-α、IL-1β 和 IL-6 的水平；以及（D-F）JB6 细胞中 TNF-α、IL-1β 和 IL-6 的水平。（+：阳性，-：阴性）。
The collagen fibers of the skin tissue were blue after MT staining. As shown in Figure 5C, which shows the collagen deposition in each subgroup after 7 days of treatment, compared with the UVB and CP groups, the collagen fibers in the LQ-CG-CP and LQ-CG-CP groups were in a tightly ordered arrangement, with smaller epithelial tissue gaps, which was similar to the normal skin tissue structure in the Control group. Although a large number of collagen fibers were also formed in the MEBO group, their arrangement and distribution were more disorderly. In Figure 5D, it is shown that collagen deposition was significantly increased in the LQ-CG-CP, LQ-CG-CP, and MEBO groups compared to the UVB group ( ). 皮肤组织的胶原纤维在 MT 染色后呈蓝色。如图 5C 所示，显示了治疗 7 天后每个亚组中的胶原沉积情况，与 UVB 和 CP 组相比， LQ-CG-CP 和 LQ-CG-CP 组的胶原纤维排列紧密有序，上皮组织间隙较小，与对照组的正常皮肤组织结构相似。尽管 MEBO 组也形成了大量胶原纤维，但它们的排列和分布更加混乱。在图 5D 中，显示了与 UVB 组相比， LQ-CG-CP， LQ-CG-CP 和 MEBO 组的胶原沉积显着增加（ ）。
2.6. Effect of LQ-CG-CP on Inflammatory Factors in a Mouse Model of Solar Dermatitis 2.6. LQ-CG-CP 对太阳皮炎小鼠模型炎症因子的影响
ELISA experiments were used to detect the effects of different LQ concentrations on the expression levels of inflammatory factors in a mouse model of solar dermatitis. As shown in Figure 6, the expression levels of inflammatory factors TNF- , IL-1 , and IL-6 were significantly increased in the UVB modeling group of mice compared with the blank control group . After 7 days of administration, the CP group could not significantly decrease the expression levels of TNF- , IL-1 , and IL-6, while the administration groups showed a significant decrease ) in the expression levels of TNF- , IL-1 , and IL-6 and alleviated the inflammatory response in a dose-dependent manner. In addition, the expression levels of IL-1 and IL-6 were lower in the LQ-CG-CP group than in the positive drug MEBO group. ELISA 实验用于检测不同 LQ 浓度对太阳皮炎小鼠模型炎症因子表达水平的影响。如图 6 所示，与空白对照组相比，UVB 模型组小鼠的炎症因子 TNF- 、IL-1 和 IL-6 的表达水平显著增加 。给药 7 天后，CP 组无法显著降低 TNF- 、IL-1 和 IL-6 的表达水平，而给药组显示出明显降低 )TNF- 、IL-1 和 IL-6 的表达水平，并且呈剂量依赖性减轻炎症反应。此外，LQ-CG-CP 组中 IL-1 和 IL-6 的表达水平低于阳性药物 MEBO 组。
B
Figure 4. The characterization results of skin tissues during the treatment process. (A) Diagram of the skin wound healing process in each group of mice (scale bar, ); (B) Skin wound healing rate in each group of mice after 7 days of treatment; and (C) Pruritus situation in mice after 7 days of treatment. ( ). 图 4. 治疗过程中皮肤组织的表征结果。 （A）小鼠各组皮肤伤口愈合过程示意图（比例尺， ）；（B）治疗 7 天后各组小鼠皮肤伤口愈合率；以及（C）治疗 7 天后小鼠的瘙痒情况。 ( )。
A
C
B
Figure 5. Results of HE and MT staining of skin wounds of mice in each group after 7 days of administration (100 ). (A) HE staining; (B) Changes in epidermal thickness of the skin; (C) MT staining; and (D) Quantification of skin collagen deposition. ( , , , magnifications, ). 图 5. 小鼠皮肤伤口在每组治疗 7 天后的 HE 染色和 MT 染色结果（100×）。（A）HE 染色；（B）皮肤表皮厚度变化；（C）MT 染色；及（D）皮肤胶原沉积量定量化。（放大倍数： ， ， ， ）。
A
B
Figure 6. Levels of inflammatory factors in mice of each group after 7 days of administration. (A) Levels of TNF- in mice of each group; (B) Levels of IL-1 in mice of each group; and (C) Levels of IL-6 in mice of each group. ( ). 图 6. 给药后每组小鼠的炎症因子水平。 (A) 每组小鼠的 TNF-α水平; (B) 每组小鼠的 IL-1β水平; 和 (C) 每组小鼠的 IL-6 水平。 ( )。
2.7. Biosafety Research 2.7. 生物安全研究
2.7.1. Histopathologic Results of Mouse Viscera 2.7.1. 小鼠内脏的组织病理学结果
After the mice in each group were given the relevant treatments, HE staining was performed on the major organs of the mice to assess the histopathological changes in each group. There were no histopathological changes in the heart, liver, spleen, lungs, and kidneys of mice in all groups compared with the Control group (Figure 7A). 在给每组小鼠进行相关治疗后，对小鼠的主要器官进行了 HE 染色，以评估每组中的组织病理学变化。与对照组相比，所有组的小鼠心脏、肝脏、脾脏、肺部和肾脏均未见组织病理学变化（图 7A）。
Figure 7. Biosafety assay. (A) HE staining results of heart, liver, spleen, lung, and kidney in each group after 7 days of treatment ( ); and (B-E) Blood biochemical indices (ALT, AST, Cr, and BUN) levels of hepatic and renal functions of mice in each group at the end of treatment. ( , magnifications, ). 图 7. 生物安全性测定。（A）处理后每组小鼠心脏、肝脏、脾脏、肺部和肾脏的 HE 染色结果（ ）；以及（B-E）每组小鼠在治疗结束时肝功能和肾功能的血液生化指标（ALT、AST、Cr 和 BUN）水平（ ，放大率 ）。
2.7.2. Blood Biochemical Indicators 2.7.2. 血液生化指标
The safety of LQ-CG-CP was further evaluated by measuring blood biochemical indices. There were no statistically significant differences in alanine aminotransferase LQ-CG-CP 的安全性通过测量血液生化指标进一步评估。丙氨酸氨基转移酶没有统计学上显著的差异。
(ALT), alanine transaminase (AST), serum creatinine (CREA), and blood urea nitrogen (BUN) in each group compared to the Control group (Figure 7B-E). （ALT）丙氨酸氨基转移酶、丙氨酸转氨酶（AST）、血清肌酐（CREA）和血尿素氮（BUN）在每组与对照组相比（图 7B-E）。
3. Discussion 3. 讨论
This study aimed to investigate whether LQ-CG-CP significantly promotes wound healing in solar dermatitis mice. The results showed that LQ-CG-CP significantly accelerated wound healing. 这项研究旨在调查 LQ-CG-CP 是否显著促进太阳皮炎小鼠的伤口愈合。结果显示，LQ-CG-CP 显著加速了伤口愈合。
Currently, sunburn dermatitis is common. In the 2005, 2010, and 2025 National Health Interview Surveys, the estimated percentage prevalence of sunburn (experiencing sunburn in the past 12 months) among U.S. adults was , and , respectively [17]. Teenagers are more likely to experience sunburn. According to an Irish research study, of school-age children (10-17 years) experienced sunburn in 2017, with reporting sunburns [18]. Ultraviolet radiation exposure is an important risk factor for skin inflammation and skin cancer, while ultraviolet overexposure and a history of associated solar dermatitis are important risk factors for skin cancer [19]. That is why the number of hospital outpatient emergency room visits to treat sunburns has increased as knowledge about the subject has become more widespread. However, there are also hospitalized sunburn patients; of sunburn patients in the Australian and New Zealand study underwent burn wound management surgery, and of these patients were admitted to the intensive care unit during their hospitalization [20]. Therefore, it is important to actively prevent or promptly treat solar dermatitis, as this can increase the risk of developing skin cancer. 目前，晒伤性皮炎很普遍。根据 2005 年、2010 年和 2025 年的全国健康采访调查，美国成年人过去 12 个月中晒伤的预计百分比分别为 、 和 [17]。青少年更有可能经历晒伤。根据一项爱尔兰研究，2017 年有 学龄儿童（10-17 岁）经历了晒伤，其中 报告了 次晒伤 [18]。紫外线辐射暴露是皮肤炎症和皮肤癌的重要风险因素，而紫外线过度暴露和相关太阳性皮炎史是皮肤癌的重要风险因素[19]。这就是为什么随着对这个主题的了解越来越广泛，治疗晒伤的医院门诊急诊就增加了。然而，也有住院治疗的晒伤患者；在澳大利亚和新西兰的研究中， 晒伤患者接受了烧伤伤口管理手术，其中{{8}}这些患者在住院期间被送进了重症监护室[20]。 因此，积极预防或及时治疗太阳性皮炎至关重要，因为这可能增加患皮肤癌的风险。
Currently, LQ is widely used in the study of various diseases. In the present study, LQ was not significantly toxic to cells at concentrations of , and , and even promoted cell proliferation at (Figure ). 目前，LQ 被广泛用于研究各种疾病。在本研究中，LQ 在浓度为 和 时对细胞没有显著毒性，甚至在 时促进了细胞增殖（图 ）。
The skin wounding process is extremely complex and consists of three main processes: inflammation, new tissue formation, and remodeling. A series of reactions such as hemostasis, inflammation, angiogenesis, growth, re-epithelialization, and tissue remodeling occur sequentially and overlappingly during these three phases [21]. One of the main hallmarks of wound healing is wound reduction [22]. During wound healing, fibroblasts migrate toward the center of the wound and transform into -SMA-positive myofibroblasts [22]. Fibroblasts of different origins are remarkably heterogeneous. Consequently, this leads to the emergence of differentially expressed genes, including extracellular matrix (ECM) synthesis, proliferation, and migration, all of which are closely related to wound healing [23]. The outermost layer of the skin is the epidermis, which is composed primarily of Keratinocytes. Fibroblasts and keratinocytes interact with each other, with fibroblasts producing signaling factors that promote the proliferation and migration of keratinocytes [24]. At present, a rapid, practical, direct, and reproducible in vitro artificial wound assay exists to determine the effect of drugs on cell migration. The wound healing assay, also known as the "cell scratch assay", is a simple, versatile, and low-cost method to study the collective cell migration and wound healing capacity [25]. In addition, wound closure from the cell scratch assay can also be used to assess wound re-epithelialization [26]. The results showed that LQ promoted cell migration and reduced the scratch wound distance, especially the fastest migration of group (Figure 2A-D). It demonstrated that LQ has the ability to promote wound reduction and accelerate the wound-healing process. 皮肤伤口愈合过程极为复杂，由三个主要过程组成：炎症、新组织形成和重塑。在这三个阶段中，出现了一系列反应，如止血、炎症、血管生成、生长、重新上皮化和组织重塑，它们按顺序和重叠地发生[21]。伤口愈合的主要特征之一是伤口减少[22]。在伤口愈合过程中，成纤维细胞向伤口中心迁移，并转化为α-SMA 阳性的肌成纤维细胞[22]。来自不同来源的成纤维细胞具有显著的异质性。因此，这导致了包括细胞外基质（ECM）合成、增殖和迁移在内的差异表达基因的出现，所有这些与伤口愈合密切相关[23]。皮肤最外层是表皮，主要由角质细胞组成。成纤维细胞和角质细胞相互作用，成纤维细胞产生信号因子促进角质细胞的增殖和迁移[24]。 目前，存在一种快速、实用、直接且可重复的体外人工伤口试验，用于确定药物对细胞迁移的影响。伤口愈合试验，也称为“细胞划痕试验”，是一种简单、多功能且低成本的方法，用于研究集体细胞迁移和伤口愈合能力[25]。此外，细胞划痕试验的伤口闭合也可以用来评估伤口重新上皮化[26]。结果显示，LQ 促进了细胞迁移并减少了划痕伤口距离，尤其是 组的迁移最快（图 2A-D）。表明 LQ 具有促进伤口减少和加速伤口愈合过程的能力。
UVB induces the release of TNF- , IL-1 , and IL-6, and its secretion is influenced by the irradiation dose (Figure 2E-J). The balance of cytokines in the wound determines the optimal state of wound healing. For example, TNF- can inhibit the differentiation of myofibroblasts, leading to prolonged inflammation and delaying wound healing to a certain extent [27]. Therefore, it is necessary to appropriately inhibit inflammatory factors. The results of this study show that LQ can effectively inhibit inflammatory factors, alleviate UVB-induced inflammatory response, and its effect is dose-dependent (Figure 3). UVB 诱导 TNF- ，IL-1 和 IL-6 的释放，其分泌受到照射剂量的影响（图 2E-J）。伤口中细胞因子的平衡决定了伤口愈合的最佳状态。例如，TNF- 可抑制肌成纤维细胞的分化，导致炎症持续时间延长，从而延迟伤口愈合一定程度 [27]。因此，适当抑制炎症因子是必要的。本研究结果显示，LQ 可以有效抑制炎症因子，缓解 UVB 诱导的炎症反应，其效果与剂量有关（图 3）。
To investigate the effect of LQ-CG-CP on mice with solar dermatitis, we also conducted in vivo studies. The successful mouse model of solar dermatitis was constructed as follows: 研究 LQ-CG-CP 对太阳性皮炎小鼠的影响，我们还进行了体内研究。成功构建太阳性皮炎小鼠模型如下：
the skin appeared red and swollen at the end of modeling, edema appeared after , and the skin was edematous and broke down after . 皮肤在造型结束时出现红肿， 后出现水肿， 后皮肤水肿并破溃。
Above all, wound healing was determined by the process of wound area change and wound healing rate. Macroscopically, the rate of wound reduction was faster in the LQ-CG-CP group as the duration of administration increased (Figure 4A). From the wound healing rate data, it can be concluded that the LQ-CG-CP and 2% LQ-CG-CP groups had a higher healing rate than the MEBO group (Figure 4B). Surprisingly, after of treatment, the LQ-CG-CP group had the best wound healing, with a complete epidermis having formed in the wound area. 首先，伤口愈合是由伤口面积变化和伤口愈合速率的过程决定的。从宏观上看，随着给药时间的增加，LQ-CG-CP 组的伤口减小速率更快（图 4A）。根据伤口愈合速率数据，可以得出结论， LQ-CG-CP 组和 2% LQ-CG-CP 组的愈合速率高于 MEBO 组（图 4B）。令人惊讶的是，在治疗 后， LQ-CG-CP 组的伤口愈合效果最好，伤口区域已完全形成表皮。
To further investigate the effect of LQ-CG-CP on wound healing, mouse skin tissues were taken for histological examination. Wound healing is closely related to granulation tissue formation, re-epithelialization, and wound reduction. Tissue damage repair begins with granulation tissue formation [28]. During the wound healing phase, granulation tissue formation occurs concurrently with re-epithelialization. Keratinocytes are the protagonists of wound healing re-epithelialization, and they can repair epidermal barrier function through proliferation and migration. After re-epithelialization occurs, the wound shrinks and produces a new epidermis. The HE results showed that LQ-CG-CP promoted reepithelialization of skin tissues; of the LQ-CG-CP group formed a complete epidermis, which was similar to the normal epidermal morphology, while the MBEO group had a disorganized epidermal layer (Figure 5A). Subsequently, collagen synthesis in vivo was also assessed in this study by MT staining. Collagen is one of the primary ECM components in the skin and is secreted primarily by fibroblasts [29]. During the proliferative phase of wound healing, -SMA-positive myofibroblasts synthesize specific ECM molecules that promote contractile remodeling of granulation tissue and facilitate wound contraction [30]. The results of MT experiments showed that LQ-CG-CP increased collagen expression and promoted collagen deposition, with the LQ-CG-CP group showing the highest collagen deposition (Figure 5C,D). This demonstrated the good crude wound healing ability of LQ-CG-CP. 为了进一步研究 LQ-CG-CP 对伤口愈合的影响，采集了小鼠皮肤组织进行了组织学检查。伤口愈合与肉芽组织形成、再上皮化和伤口缩小密切相关。组织损伤修复始于肉芽组织的形成[28]。在伤口愈合阶段，肉芽组织的形成与再上皮化同时发生。角质细胞是伤口愈合再上皮化的主角，并且它们通过增殖和迁移修复表皮屏障功能。再上皮化后，伤口收缩并产生新的表皮。HE 结果显示，LQ-CG-CP 促进了皮肤组织的再上皮化；LQ-CG-CP 组中 形成了完整的表皮，类似于正常的表皮形态，而 MBEO 组的表皮层混乱（图 5A）。随后，通过 MT 染色也评估了体内胶原蛋白的合成。胶原蛋白是皮肤中的主要 ECM 成分之一，主要由成纤维细胞分泌[29]。 在伤口愈合的增殖期间， -SMA 阳性的肌成纤维细胞合成特定的 ECM 分子，促进了肉芽组织的收缩重塑并促进了伤口的收缩[30]。MT 实验的结果显示，LQ-CG-CP 增加了胶原蛋白的表达并促进了胶原蛋白的沉积，其中 LQ-CG-CP 组显示了最高的胶原蛋白沉积（图 5C，D）。这表明了 LQ-CG-CP 良好的粗糙伤口愈合能力。
UVB promotes the production and release of inflammatory factors (TNF- , IL-1 , and IL-6) to induce an inflammatory response. TNF- , IL-1 , and IL-6 affect the proliferation and differentiation of keratinocytes as well as ECM formation [31]. While prolonged inflammation can prolong wound healing, it can also lead to the development of keloids or hyperplastic scars [32,33]. In addition, both the initiating signals for transcription of immature IL-1 and the generation of danger signals for the release of mature IL-1 lead to a macrophage-induced inflammatory response that dysregulates wound healing [34]. The results showed that LQ-CG-CP reduced the inflammatory response and inhibited the side effects associated with long-term inflammation (Figure 6). Moreover, LQ-CG-CP has been shown to have no side effects on mice in biosafety tests (Figure 7). UVB 促进炎症因子（TNF- ，IL-1 和 IL-6）的产生和释放，诱导炎症反应。TNF- ，IL-1 和 IL-6 影响角质细胞的增殖和分化以及 ECM 形成[31]。长期的炎症会延长伤口愈合时间，还可能导致瘢痕或增生性瘢痕的发展[32,33]。此外，未成熟 IL-1 的转录启动信号以及成熟 IL-1 释放的危险信号的产生都会导致巨噬细胞诱导的炎症反应失调伤口愈合[34]。结果显示，LQ-CG-CP 减少了炎症反应，并抑制了与长期炎症相关的副作用（图 6）。此外，生物安全性测试表明，LQ-CG-CP 对小鼠没有副作用（图 7）。
Sunburned skin, in addition to inflammation and skin damage, is characterized by intense itching, and the itching associated with sunburn is known as the "Hell's Itch" [35]. This itching seriously affects the quality of life and must be effectively intervened. Cold compresses or cold showers can relieve itching [36]. This study also combined cold therapy for administration to reduce discomfort at the skin lesions. The decrease in the number of scratches of mice in the CP group compared with the UVB group, as well as the fact that the number of scratches in the LQ-CG-CP group was less than that in the LQ-CG group, could indicate that cold compresses could alleviate the itching symptom of mice (Figure 4C). However, the mechanism of UVB-induced itching is not fully understood. It has been studied that UVB irradiation induces pruritus in mice by promoting TRPV1 channel function in dorsal root ganglion neurons [37]. Future studies could delve deeper into the mechanisms of sunburn-related itching and the effects that interventions have on the mechanisms. 晒伤的皮肤除了炎症和损伤外，还以剧烈瘙痒为特征，与晒伤相关的瘙痒被称为“地狱痒”。这种瘙痒严重影响生活质量，必须进行有效干预。冷敷或冷水淋浴可以缓解瘙痒。本研究还结合了冷疗进行管理，以减轻皮损的不适。与 UVB 组相比，CP 组小鼠的抓挠次数减少，而 LQ-CG-CP 组的抓挠次数少于 LQ-CG 组，这可能表明冷敷可以缓解小鼠的瘙痒症状。然而，UVB 诱导的瘙痒机制尚未完全理解。研究表明，UVB 照射通过促进脊髓背根神经节神经元中 TRPV1 通道的功能而诱发小鼠的瘙痒。未来的研究可以深入探讨晒伤相关瘙痒的机制以及干预措施对机制的影响。
4. Materials and Methods 4. 材料和方法
4.1. Cell Culture and Treatment 4.1. 细胞培养和处理
The human epidermal keratinocyte (HaCaT) cell line was taken from Suyan Biotechnology (Guangzhou, China), and the mouse epidermal JB6 cell line was obtained from Yiyou Biotechnology (Guangzhou, China). HaCaT cells were cultured in Dulbecco's modified Eagle's medium (DMEM, GIBCO, Grand Island, NE, USA) containing fetal bovine serum (FBS, BIOIND, Kibbutz Beit Haemek, Israel) and antibiotics ( penicillin and streptomycin, GIBCO, Grand Island, NE, USA), while JB6 cells were cultured in Roswell Park Memorial Institute (RPMI) 1640 (GIBCO, Grand Island, NE, USA) containing FBS and antibiotics ( penicillin and streptomycin, GIBCO, Grand Island, NE, USA). These cells were cultured at with a incubator. 人类表皮角质形成细胞（HaCaT）细胞系来源于苏研生物技术（中国广州），小鼠表皮 JB6 细胞系来源于亿友生物技术（中国广州）。HaCaT 细胞在含有 胎牛血清（FBS，以色列 Kibbutz Beit Haemek 的 BIOIND）和抗生素（ 青霉素和 链霉素，美国内布拉斯加州大岛的 GIBCO）的杜氏改良的鹰的培养基（DMEM，GIBCO，美国内布拉斯加州大岛）中培养，而 JB6 细胞在罗斯韦尔帕克纪念研究所（RPMI）1640（GIBCO，美国内布拉斯加州大岛）中含有 FBS 和抗生素（ 青霉素和 链霉素，GIBCO，美国内布拉斯加州大岛）中培养。这些细胞在 与 孵育器中培养。
LQ (Purity , CAS: 551-15-5) was purchased from Chengdu nakeli Biotechnology Co., Ltd. (Chengdu, China). The structural formula of LQ is provided in the Supplementary Materials (Figure S1). LQ was dissolved in dimethyl sulfoxide (DMSO, Sigma, St. Louis, MO, USA). The final concentration of DMSO was , which had no significant effect on cell viability, as detailed in Supplementary Figure S2. LQ（纯度 ，CAS：551-15-5）由成都那克利生物技术有限公司（中国成都）购买。LQ 的结构式见附加材料（图 S1）。LQ 溶解于二甲基亚砜（DMSO，Sigma，美国密苏里州圣路易斯）。DMSO 的最终浓度为 ，对细胞活力没有显著影响，详见附加图 S2。
A UVB light source (Guanhongrui, Shenzhen, China) was used in this study, providing UV light in the range of , with its spectral energy mainly concentrated at . At the distance of , the average UVB irradiation intensity was . 本研究 B 光源（中国深圳市冠宏锐）用于本研究，提供波长范围内的紫外光，主要集中在 ，距离 处中在 。在 的距离上，平均 UVB 辐射强度为 。
4.2. Cell Viability Assay 4.2. 细胞活力测定
The MTT assay was used to test cell viability. The cells were digested down with trypsin and prepared into cell suspensions. After the cells were counted, a cell suspension was prepared at a concentration of cells per well, and then of each well was seeded in a 96 -well plate. After incubation, the old medium was discarded and fresh medium was added, followed by UVB at different irradiation doses , ; or cells were cultured with different concentrations of , ) for . Then, cells were incubated for by adding of MTT (Rsbio, Shanghai, China) per well. After that, the MTT mixture was discarded, and of DMSO was added to each well, and the plate was shaken on a shaker for . Later, the absorbance at was measured for each group using the Microplate Reader (Biotek, Winooski, VT, USA). MTT 检测法被用来测试细胞的存活率。细胞被胰蛋白酶消化并制备成细胞悬液。细胞计数后，每个孔制备细胞悬液浓度为 个细胞/孔，然后每个孔种植到 96 孔板中 。孵育 后，旧培养基被丢弃，加入新培养基，随后以不同的紫外线 B 辐射剂量 ， ；或者用不同浓度的 ， ）培养细胞 。然后，通过在每个孔中加入 MTT（Rsbio,上海，中国），细胞被孵育 。然后，废弃 MTT 混合物，并向每个孔中加入 DMSO，并在振荡器上振荡 。之后，使用微板阅读器（Biotek，Winooski，VT，美国）测量每组在 处的吸光度。
4.3. Cell Migration Assay 4.3. 细胞迁移实验
HaCaT cells and JB6 cells ( cells/well) were seeded in a six-well plate for the wound healing assay. When the cells were cultured to confluence, the cells were pretreated with a low dose of mitomycin c ( ) for . After removing the mitomycin c-containing medium and washing it once with PBS, a straight line was drawn vertically with a 200 uL pipette tipper well. Dropped cells were washed out with phosphatebuffered saline (PBS, Meilunbio, Dalian, China). And then, DMEM containing different concentrations of LQ was added to each well. Groups of scratched areas were photographed at and using a microscope (Olympus, Tokyo, Japan). The scratch wound closure rate was determined by the following equation: Scratch wound closure rate Scratch area at Scratch area at Scratch area at . HaCaT 细胞和 JB6 细胞（ 个细胞/孔）被种植在六孔板中用于伤口愈合实验。当细胞培养至 的时候，细胞被预处理与一低剂量的丝裂霉素 C（ ）处理 。去除含有丝裂霉素 C 的培养基后，用 PBS 洗涤一次，然后用一个 200μL 移液器在每个孔上垂直地画一条直线。用磷酸盐缓冲液（PBS，美仑生物，中国大连）冲洗掉滴落的细胞。然后，向每个孔中加入含有不同浓度 LQ 的 DMEM。在 和 使用显微镜（奥林巴斯，日本东京）拍摄不同组划痕区域的照片。刮痕愈合率由以下方程确定：刮痕愈合率 刮痕区域在 刮痕区域在 刮痕区域在 。
4.4. Preparation of 4.4. 的准备
Carbomer 940 gel does not cause skin irritation and is the vehicle for the drug application in this article. First, of carbomer 940 powder (Meilunbio, Dalian, China) was mixed with of ultrapure water and stirred for , and then the was adjusted to 7.0 with triethanolamine (Macklin, Shanghai, China). Subsequently, three different concentrations of LQ were added to formulate a carbomer gel containing , and LQ. The previous step requires stirring at until a homogeneous and good-quality gel is formed [38]. What is more, cold paste (Haixu, Rizhao, China) is pre-made. LQ-CG-CP was prepared by uniformly applying LQ-containing carbomer gel to the cold paste. Its 940 凝胶不会引起皮肤刺激，并且是本文中药物应用的载体。首先，将 940 聚合物粉（美伦生物，大连，中国）的 与超纯水的 混合搅拌 ，然后用三乙醇胺（麦克林，上海，中国）调节 至 7.0。随后，添加三种不同浓度的 LQ 以制备 聚合物凝胶，其中包含 和 的 LQ。前述制备步骤需要搅拌 直到形成均匀且优质的凝胶[38]。此外，冷膏（海旭，日照，中国）已经预先制备好。通过均匀涂抹含 LQ 的聚合物凝胶来制备 LQ-CG-CP。
relevant characterization and in vitro drug release assays can be found in Figures S3 and S4 of the Supplementary Materials. 相关特征描述和体外药物释放实验可在补充材料的图 S3 和图 S4 中找到。
4.5. Establishment and Treatment of Mouse Solar Dermatitis Model 4.5. 小鼠太阳性皮炎模型的建立和处理
All experimental animal procedures were carried out following the Guidelines for the Care and Use of Laboratory Animals at Guangdong Pharmaceutical University and approved by the Animal Ethics Committee (No. gdpulacspf2022092). 8 w BALB/c female mice were purchased from Guangdong Laboratory Animal Center. The experimental animals were housed at a temperature of and humidity of , kept in alternating light and dark for . Feed, drinking water, and bedding were changed regularly. Mice were first adapted to rearing for , and dorsal dehairing was performed the night before modeling. Except for the control group, the rest of the mice were exposed to UVB light irradiation. The UVB irradiation dose is (About ). After , mice were divided into the UVB group, LQ-CG group, LQ-CG-CP group, LQ-CG-CP group, 2% LQ-CG-CP group, and positive drug group (MEBO, Shantou, China). According to the grouping, the corresponding dose was given externally on the skin of mice once a day for 7 days. At the same time, the skin of the mice was photographed and recorded at the same height every day. The size of skin wounds in mice was measured using Image J software (Version 1.80; NIH, Bethesda, MD, USA), and wound healing rates were calculated. Moreover, at the end of the treatment, the mice were placed in transparent boxes and videotaped for one hour to record the scratching frequency of the mice. After of treatment, mice were anesthetized with isoflurane and then sacrificed, and skin tissues and major organ tissues were removed. 所有实验动物程序均遵循广东药科大学实验动物护理和使用指南，并获得动物伦理委员会批准（编号 gdpulacspf2022092）。8 只 8 周大的雌性 BALB/c 小鼠从广东省实验动物中心购买。实验动物的温度和湿度保持在 和 ，交替光照和黑暗保持 。饲料、饮水和寝具定期更换。小鼠首先适应饲养 ，并在模型制备前一晚进行背部脱毛。除对照组外，其余小鼠暴露于 UVB 光照。UVB 照射剂量为 （约 ）。过了 后，小鼠分为 UVB 组、 LQ-CG 组、 LQ-CG-CP 组、 LQ-CG-CP 组、2% LQ-CG-CP 组和阳性药物组（MEBO，中国汕头）。根据分组，每日在小鼠皮肤外给予相应剂量，持续 7 天。同时，每天以相同高度拍摄和记录小鼠皮肤情况。 小鼠皮肤伤口的大小使用 Image J 软件（版本 1.80；NIH，美国马里兰州贝塞斯达）测量，并计算伤口愈合速率。此外，治疗结束时，小鼠被放置在透明箱中，并录制了一小时的视频以记录小鼠的搔抓频率。治疗 后，小鼠用异氟醚麻醉，然后被牺牲，取出皮肤组织和主要器官组织。
ELISA kits (Jiangsu Meimian Industrial Co., Ltd., Yancheng, China) were used to detect the secretory levels of TNF- , IL-1 , and IL-6. Supernatants were collected from JB6 and cells after of UVB irradiation or of UVB irradiation followed by of incubation with LQ. Serum was extracted from mice with a model of solar dermatitis given LQ for . According to the manufacturer's instructions, supernatants and serum were used to detect the expression of relevant indicators. ELISA 试剂盒（中国江苏美眠实业有限公司，盐城）用于检测 TNF-α、IL-1β和 IL-6 的分泌水平。在 UVB 照射 后，从 JB6 和 细胞收集上清液，或在 UVB 照射 后，用 LQ 培养 后收集上清液。从接受 LQ 治疗的太阳性皮炎模型小鼠中提取血清，持续 。根据制造商的说明，上清液和血清用于检测相关指标的表达。
4.7. Histopathological Examination 4.7. 组织病理学检查
After the skin tissues were taken, they were fixed in 4% paraformaldehyde (Biosharp, Bengbu, China) for , embedded and deparaffinized, and then stained with hematoxylin and eosin (HE). In addition, skin tissues were stained for Masson's trichrome (MT). Pathologic changes in skin tissue were observed through the microscope. Later, epidermal thickness and collagen deposition quantification (Collagen deposition quantification Collagen area/Total organizational area ) were measured using Image J software (Version 1.80; , Bethesda, MD, USA). 皮肤组织取材后，用 4%甲醛固定（Biosharp，中国蚌埠）， 后，包埋、去蜡，然后用苏木精和伊红（HE）染色。此外，皮肤组织还进行了 Masson 三色染色（MT）。通过显微镜观察皮肤组织的病理变化。随后，使用 Image J 软件（版本 1.80； ，美国马里兰州贝塞斯达）测量表皮厚度和胶原沉积定量（胶原沉积定量 胶原区域/总组织区域 ）。
4.8. Biosafety Validation 4.8. 生物安全验证
Following the steps above, the major organs of mice were taken for histopathological analysis. In addition, serum samples from mice were used for biochemical assays, which contained four indicators: ALT, AST, Cr, and BUN. The levels of ALT, AST, Cr, and BUN were measured according to the kit manufacturer's instructions (Nanjing Jiancheng, Nanjing, China). 根据上述步骤，取出了小鼠的主要器官进行了组织病理学分析。此外，使用小鼠的血清样本进行了生化分析，其中包含四个指标：ALT、AST、Cr 和 BUN。ALT、AST、Cr 和 BUN 的水平是根据试剂盒制造商的说明书进行测量的（南京建成，中国南京）。
4.9. Statistical Analysis 4.9. 统计分析
Results were shown as the mean standard deviation (SD). Statistical significance was assessed by -test or one-way ANOVA using Graph Pad Prism 8.0 software. Comparisons of more than two groups were corrected using the Bonferroni test. indicates statistical significance. All experiments were repeated three times. 结果显示为均值 标准差（SD）。统计学上的显著性是通过 -检验或单因素方差分析使用 Graph Pad Prism 8.0 软件进行评估。对比多于两组的情况使用 Bonferroni 校正法。 表示统计学上的显著性。所有实验均重复三次。
5. Conclusions 5. 结论
In this study, we evaluated the therapeutic efficacy of LQ-CG-CP in solar dermatitis. LQ-CG-CP inhibits inflammatory reactions, reduces itching symptoms, promotes collagen production, and promotes wound healing. In conclusion, LQ-CG-CP shows great potential in the treatment of solar dermatitis and deserves further research. 在这项研究中，我们评估了 LQ-CG-CP 在太阳性皮炎治疗中的疗效。 LQ-CG-CP 抑制炎症反应，减轻瘙痒症状，促进胶原蛋白生产，并促进伤口愈合。 总之，LQ-CG-CP 在太阳性皮炎治疗中显示出很大潜力，并值得进一步研究。
Supplementary Materials: The following supporting information can be downloaded at: https:/ /www. mdpi.com/article/10.3390/ijms25073767/s1. 补充材料：以下支持信息可下载：https://www.mdpi.com/article/10.3390/ijms25073767/s1。
Author Contributions: Y.H.: Formal analysis, Methodology, Writing-original draft, Conducted most of the in vivo experiments. S.L.: Formal analysis, Conceptualization, Data curation, Conducted most of the in vitro experiments. J.P.: Formal analysis, Methodology. C.S.: Formal analysis. W.C.: Writing-review and editing, Supervision, Project administration. Y.Z.: Conceptualization, Methodology, Writing-review and editing, Funding acquisition. All authors have read and agreed to the published version of the manuscript. 作者贡献：Y.H.：正式分析，方法论，写作原稿，进行了大部分体内实验。S.L.：正式分析，概念化，数据整理，进行了大部分体外实验。J.P.：正式分析，方法论。C.S.：正式分析。W.C.：写作审查和编辑，监督，项目管理。Y.Z.：概念化，方法论，写作审查和编辑，资金获取。所有作者已阅读并同意了手稿的已发表版本。
Funding: This research has been supported by grants from the Guangzhou Basic and Applied Basic Research Project (grant number 202201010663 belong to Yun Zhang) and the Guangdong Provincial Bureau of Traditional Chinese Medicine Project (grant number 20241176 belong to Yun Zhang). 资金：本研究得到了广州市基础与应用基础研究项目（项目编号 202201010663，由张云拥有）和广东省中医药管理局项目（项目编号 20241176，由张云拥有）的资助。
Institutional Review Board Statement: The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Animal Ethics Committee of Guangdong Pharmaceutical University (No. gdpulacspf2022092). 机构审查委员会声明：该研究按照赫尔辛基宣言的指导方针进行，并获得了广东药科大学动物伦理委员会的批准（批准号为 gdpulacspf2022092）。
Informed Consent Statement: Not applicable. 知情同意声明：不适用。
Data Availability Statement: The data that support the findings of this study are available from the corresponding author upon reasonable request. 数据可用性声明：本研究的支持数据可根据合理请求从对应作者处获得。
Acknowledgments: We thank the Care and Use of Laboratory Animals of Guangdong Pharmaceutical University for providing us with space to keep animals. 致谢：我们感谢广东药科大学实验动物使用与保护中心为我们提供了动物饲养的空间。
Conflicts of Interest: The authors declare no conflicts of interest. 利益冲突：作者声明没有利益冲突。
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