Smith Jacob F, Starr Evan G, Goodman Michael A, Hanson Romney B, Palmer Trent A, Woolstenhulme Jonathan B, Weyand Jeffery A, Marchant Andrew D, Bueckers Shawen L, Nelson Tanner K, Sterling Matthew T, Rose Brandon J, Porter James P, Eggett Dennis L, Kooyman David L
Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT, United States.
Statistics, Brigham Young University, Provo, UT, United States.
Front Physiol. 2020 Feb 18;11:80. doi: 10.3389/fphys.2020.00080. eCollection 2020.
Osteoarthritis (OA) is a degenerative joint disease characterized by inflammatory degradation of articular cartilage and subchondral bone. Wogonin, a compound extracted from the plant (colloquially known as skullcap), has previously been shown to have direct anti-inflammatory and antioxidative properties. We examined the pain-reducing, anti-inflammatory, and chondroprotective effects of wogonin when applied as a topical cream. We validated the efficacy of delivering wogonin transdermally in a cream using pig ear skin in a Franz diffusion system. Using a surgical mouse model, we examined the severity and progression of OA with and without the topical application of wogonin. Using a running wheel to track activity, we found that mice with wogonin treatment were statistically more active than mice receiving vehicle treatment. OA progression was analyzed using modified Mankin and OARSI scoring and direct quantification of cyst-like lesions at the chondro-osseus junction; in each instance we observed a statistically significant attenuation of OA severity among mice treated with wogonin compared to the vehicle treatment. Immunohistochemistry revealed a significant decrease in protein expression of transforming growth factor β1 (TGF-β1), high temperature receptor A1 (HTRA1), matrix metalloprotease 13 (MMP-13) and NF-κB in wogonin-treated mice, further bolstering the cartilage morphology assessments in the form of a decrease in inflammatory and OA biomarkers.
骨关节炎（OA）是一种退行性关节疾病，其特征是关节软骨和软骨下骨发生炎症性退变。汉黄芩素是从植物（俗称黄芩）中提取的一种化合物，此前已被证明具有直接的抗炎和抗氧化特性。我们研究了将汉黄芩素制成外用乳膏时的止痛、抗炎和软骨保护作用。我们在Franz扩散系统中使用猪耳皮肤验证了在乳膏中经皮递送汉黄芩素的有效性。使用手术小鼠模型，我们研究了局部应用汉黄芩素和未应用汉黄芩素时OA的严重程度和进展情况。使用跑步轮跟踪活动情况，我们发现接受汉黄芩素治疗的小鼠在统计学上比接受赋形剂治疗的小鼠更活跃。使用改良的Mankin评分和OARSI评分以及对软骨-骨交界处的囊肿样病变进行直接定量分析OA进展；在每种情况下，我们观察到与赋形剂治疗相比，接受汉黄芩素治疗的小鼠的OA严重程度在统计学上有显著降低。免疫组织化学显示，在接受汉黄芩素治疗的小鼠中，转化生长因子β1（TGF-β1）、高温受体A1（HTRA1）、基质金属蛋白酶13（MMP-13）和核因子κB（NF-κB）的蛋白表达显著降低，进一步支持了以炎症和OA生物标志物减少形式的软骨形态学评估。
