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疏风解毒胶囊通过 AMPK/mTOR 自噬通路改善变应性鼻炎小鼠的嗅觉功能障碍。

Shufeng Jiedu capsule ameliorates olfactory dysfunction via the AMPK/mTOR autophagy pathway in a mouse model of allergic rhinitis.

机构信息

Department of Otorhinolaryngology Head and Neck Surgery, the Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230601, China.

Department of Pharmacology, School of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, China.

出版信息

Phytomedicine. 2022 Dec;107:154426. doi: 10.1016/j.phymed.2022.154426. Epub 2022 Sep 2.

DOI:10.1016/j.phymed.2022.154426
PMID:36116201
Abstract

BACKGROUND

Shufeng Jiedu capsule (SFJDC) has been widely used as a conventional Chinese pharmaceutical agent for various upper respiratory infections, including acute lung injury, acute respiratory distress syndrome and allergic rhinitis (AR). However, its mechanism in AR remains unclear.

PURPOSE

The present study aimed to decipher the antiallergic inflammatory effect of SFJDC in an AR model with olfactory dysfunction. Specifically, we wanted to explore whether SFJDC can improve the olfactory abnormality in AR mice and reduce the levels of inflammatory factors in the olfactory epithelium (OE) and olfactory bulb (OB).

METHODS

To address the above issues, we constructed an AR model using C57BL/6 mice, which were sensitised and challenged with ovalbumin (OVA) by intraperitoneal injection. SFJDC (0.045 or 0.18 g/kg) was delivered by gavage administration 1 h prior to the intraperitoneal injection of OVA. The control mice received saline alone. Then, the animals were assessed according to the presence of nasal symptoms and nasal inflammation, and a buried food test was used to evaluate olfactory function. The levels of proteins involved in the AMPK/mTOR autophagy pathway in the OE and OB were investigated by western blotting and fluorescence staining.

RESULTS

After OVA induction of AR and drug administration, we found that SFJDC significantly ameliorated the nasal symptoms and allergic inflammatory reaction of the nasal mucosa superior to cetirizine. A behavioural test indicated that the mice with AR had olfactory dysfunction, and SFJDC can ameliorate this behavior deficiency. Meanwhile, SFJDC clearly reduced the neuroinflammation level in OE tissue. In addition, SFJDC increased p-mTOR and decreased p-AMPK, beclin1, LC3 and cleaved caspase-3 levels in the OE.

CONCLUSIONS

In addition to antibacterial and antiviral activities, SFJDC has marked anti-inflammatory effects in AR mice. Its mechanism of action in the nasal cavity involves inhibition of upregulated anti-inflammatory cytokines, modulation of autophagy and apoptosis levels and regulation of autophagy through the AMPK/mTOR pathway in the OE tissue of AR mice. Hence, SFJDC is a promising drug for AR, and clinical trials should further validate the therapeutic impact of SFJDC on AR with olfactory dysfunction.

摘要

背景

疏风解毒胶囊 (SFJDC) 已被广泛用作治疗各种上呼吸道感染的常规中药制剂,包括急性肺损伤、急性呼吸窘迫综合征和过敏性鼻炎 (AR)。然而,其在 AR 中的作用机制尚不清楚。

目的

本研究旨在破译 SFJDC 在嗅觉功能障碍的 AR 模型中的抗过敏抗炎作用。具体来说,我们想探讨 SFJDC 是否可以改善 AR 小鼠的嗅觉异常,并降低嗅上皮 (OE) 和嗅球 (OB) 中炎症因子的水平。

方法

为了解决上述问题,我们使用 C57BL/6 小鼠构建了 AR 模型,通过腹腔注射卵清蛋白 (OVA) 对其进行致敏和攻毒。SFJDC(0.045 或 0.18 g/kg)通过灌胃给药,在腹腔注射 OVA 前 1 小时给药。对照组小鼠给予生理盐水。然后,根据鼻症状和鼻黏膜炎症的存在对动物进行评估,并使用埋藏食物测试评估嗅觉功能。通过 Western blot 和荧光染色法研究 OE 和 OB 中 AMPK/mTOR 自噬通路相关蛋白的水平。

结果

在 AR 和药物给药后 OVA 诱导后,我们发现 SFJDC 明显改善了比西替利嗪更好的鼻症状和鼻黏膜过敏炎症反应。行为测试表明,AR 小鼠存在嗅觉功能障碍,SFJDC 可改善这种行为缺陷。同时,SFJDC 明显降低了 OE 组织中的神经炎症水平。此外,SFJDC 增加了 OE 中的 p-mTOR,并降低了 p-AMPK、beclin1、LC3 和 cleaved caspase-3 水平。

结论

除了具有抗菌和抗病毒活性外,SFJDC 在 AR 小鼠中还具有显著的抗炎作用。其在鼻腔中的作用机制涉及抑制上调的抗炎细胞因子,调节自噬和细胞凋亡水平,并通过 AR 小鼠 OE 组织中的 AMPK/mTOR 通路调节自噬。因此,SFJDC 是一种有前途的 AR 药物,临床试验应进一步验证 SFJDC 对伴有嗅觉功能障碍的 AR 的治疗作用。

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