Innovative Chinese Medicine Research Institute, Engineering Research Center of Modern Preparation Technology of Traditional Chinese Medicine, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Center for Drug Safety Evaluation, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
J Ethnopharmacol. 2020 Jun 12;255:112773. doi: 10.1016/j.jep.2020.112773. Epub 2020 Mar 18.
Fructus Arctii is the dried ripe fruit of Arctium lappa L. (family Asteraceae). It is a well-known Chinese Materia Medica that was included in the Chinese pharmacopoeia because of its traditional therapeutic actions, such as heat removal, detoxification, and elimination of swelling. Since ancient times Fructus Arctii has been used extensively in a number of classical drug formulas to treat type 2 diabetes mellitus. Modern pharmacological studies have shown that certain components of Fructus Arctii have multiple physiological activities on type 2 diabetes and its complications.
We have reported the inhibitory effect of total lignans from Fructus Arctii (TLFA) on aldose reductase, the key enzyme in the polyol pathway, which is considered to be closely related to the onset of diabetic retinopathy (DR). The present study aimed to observe the preventive and therapeutic effects of TLFA on DR in Streptozotocin (STZ)-induced DR rats.
TLFA was prepared from Fructus Arctii and its content was determined using UV spectrophotometry. The DR model was induced by STZ in Wistar rats. For DR prevention, the animals were gavaged once daily for 9 weeks with TLFA (1.38, 0.69, and 0.35 g/kg/day) as soon as they were confirmed as diabetes models. Pathological changes to retinal tissues and the expression of vascular endothelial growth factor (VEGF) and protein kinase C (PKC) in the retina were detected after TLFA treatment. The effects of TLFA on blood glucose levels and body weight were also observed. For DR treatment, the animals were gavaged once daily for 12 weeks with TLFA (1.38 and 0.69 g/kg/day) at 3 months after they were confirmed as diabetes models. The therapeutic effect was studied using quantitative detection of blood-retina barrier (BRB) breakdown via an Evans Blue leakage assay.
For DR prevention, after 9 weeks of TLFA administration, histopathological examination of retinal tissue showed that TLFA improved the lesions in the retina. Changes to retinal microstructures such as capillaries, ganglion cells, bipolar cells, and the membrane disk examined by electron microscopy further confirmed that TLFA has a preventive effect on retinopathy. Terminal deoxynucleotidyl Transferase-mediated dUTP nick end labeling (TUNEL) detection showed that TLFA could inhibit retinal cell apoptosis in the diabetic rats, and fasting blood glucose (FBG) levels of rats in the TLFA-treated groups decreased during the experiment. For DR treatment, after 3 months of administration, the amount of dye leakage in the TLFA-administered groups was reduced by more than 50% compared with that in the model group, which indicated that TLFA has a therapeutic effect on middle and late DR. Messenger RNA (mRNA) expression of VEGF and PKCβ2 in the retina detected by real-time fluorescent quantitative reverse transcription-polymerase chain reaction (FQ-RT-PCR) showed that TLFA could inhibit the expression of them, which was consistent with the results of immunohistochemistry (IHC).
TLFA has a preventive and therapeutic effect on DR. Its mechanism of action on DR is related to inhibiting PKC activation and blocking VEGF elevation.
牛蒡子是菊科牛蒡属植物牛蒡（L.）的干燥成熟果实。它是一种著名的中药，由于其传统的治疗作用，如清热、解毒和消肿，被列入中国药典。自古以来，牛蒡子就被广泛应用于许多经典方剂中，用于治疗 2 型糖尿病。现代药理学研究表明，牛蒡子的某些成分对 2 型糖尿病及其并发症具有多种生理活性。
我们已经报道了牛蒡子总木脂素（TLFA）对醛糖还原酶的抑制作用，醛糖还原酶是多元醇途径中的关键酶，被认为与糖尿病性视网膜病变（DR）的发病密切相关。本研究旨在观察 TLFA 对链脲佐菌素（STZ）诱导的 DR 大鼠 DR 的预防和治疗作用。
TLFA 从牛蒡子中提取，采用紫外分光光度法测定其含量。DR 模型通过 STZ 在 Wistar 大鼠中诱导。对于 DR 的预防，一旦动物被确认为糖尿病模型，就每天用 TLFA（1.38、0.69 和 0.35 g/kg/天）灌胃 9 周。TLFA 治疗后，检测视网膜组织的病理变化以及血管内皮生长因子（VEGF）和蛋白激酶 C（PKC）在视网膜中的表达。还观察了 TLFA 对血糖水平和体重的影响。对于 DR 的治疗，在动物被确认为糖尿病模型 3 个月后，每天用 TLFA（1.38 和 0.69 g/kg/天）灌胃 12 周。通过 Evans Blue 渗漏测定定量检测血视网膜屏障（BRB）的破坏来研究治疗效果。
对于 DR 的预防，TLFA 给药 9 周后，视网膜组织的组织病理学检查显示 TLFA 改善了视网膜病变。电镜下观察到的视网膜微血管、节细胞、双极细胞和膜盘等视网膜超微结构的变化进一步证实 TLFA 对视网膜病变具有预防作用。末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记（TUNEL）检测显示，TLFA 可抑制糖尿病大鼠视网膜细胞凋亡，TLFA 治疗组大鼠在实验过程中空腹血糖（FBG）水平下降。对于 DR 的治疗，给药 3 个月后，TLFA 给药组的染料渗漏量比模型组减少了 50%以上，表明 TLFA 对中晚期 DR 具有治疗作用。实时荧光定量逆转录聚合酶链反应（FQ-RT-PCR）检测到视网膜中 VEGF 和 PKCβ2 的信使 RNA（mRNA）表达表明，TLFA 可抑制其表达，这与免疫组织化学（IHC）的结果一致。
TLFA 对 DR 具有预防和治疗作用。其对 DR 的作用机制与抑制 PKC 激活和阻断 VEGF 升高有关。
