Innovative Engineering Research Center of Veterinary Pharmaceutics, Department of Pharmacy, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Sichuan Academy of Chinese Medicine Sciences, Chengdu, Sichuan 610041, China.
Innovative Engineering Research Center of Veterinary Pharmaceutics, Department of Pharmacy, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, China.
Biomed Pharmacother. 2022 Dec;156:113888. doi: 10.1016/j.biopha.2022.113888. Epub 2022 Oct 19.
Acute lung injury (ALI), a clinical syndrome of acute respiratory failure due to acute lung inflammation, remains a substantial public health problem in the worldwide. Ligusticum Chuanxiong Rhizoma and Angelicae Sinensis Radix was herb-pair of the traditional Chinese medicine. Modern pharmacological studies have shown that volatile oil extracted from Chuanxiong Rhizome and Angelicae Sinensis Radix is identified as an important active ingredient, which has good antipyretic, analgesic and anti-inflammatory effects. However, whether their volatile oil combination (CA-VO), has effects on the prevention and treatment of ALI has not been reported yet. Due to poor water solubility and low oral bioavailability of CA-VO, CA -VO-loaded microemulsion (CA-VO-ME) was formulated to enhance its oral bioavailability. The physical properties of CA-VO-ME were characterized. The pharmacokinetic parameters and the effect on ALI were evaluated. The particle size, polydispersity index, zeta potential, and encapsulation efficiency of CA-VO-ME were 20.19 ± 0.08 nm, 0.091 ± 0.01, 36.33 ± 4.29%, and 93.75%, respectively. CA-VO-ME had a greater bioavailability (214%) than CA-VO. CA-VO-ME reduced the lipopolysaccharide (LPS)-induced increase in levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in vitro and/or in vivo. Moreover, CA-VO-ME treatment notably decreased the lung index, ameliorated histopathological changes and prolonged the survival of ALI mice. By comparison, CA-VO-ME exerted a better effect on ALI than CA-VO, suggesting that CA-VO-ME is a promising drug for the treatment of ALI.
急性肺损伤(ALI)是一种因急性肺炎症导致急性呼吸衰竭的临床综合征,在全球范围内仍是一个重大的公共卫生问题。川芎和当归是中药的药对。现代药理学研究表明,从川芎根茎和当归中提取的挥发油被鉴定为一种重要的活性成分,具有良好的解热、镇痛和抗炎作用。然而,它们的挥发油混合物(CA-VO)是否对 ALI 的预防和治疗有作用尚未有报道。由于 CA-VO 的水溶性差和口服生物利用度低,因此制备了 CA-VO 载药微乳(CA-VO-ME)以提高其口服生物利用度。对 CA-VO-ME 的物理性质进行了表征。评价了 CA-VO-ME 的药代动力学参数和对 ALI 的作用。CA-VO-ME 的粒径、多分散指数、Zeta 电位和包封效率分别为 20.19±0.08nm、0.091±0.01、36.33±4.29%和 93.75%。CA-VO-ME 的生物利用度(214%)大于 CA-VO。CA-VO-ME 降低了脂多糖(LPS)诱导的一氧化氮(NO)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、诱导型一氧化氮合酶(iNOS)和环氧化酶-2(COX-2)水平的升高,无论是在体外还是体内。此外,CA-VO-ME 治疗明显降低了 ALI 小鼠的肺指数,改善了组织病理学变化并延长了其生存时间。相比之下,CA-VO-ME 对 ALI 的作用优于 CA-VO,这表明 CA-VO-ME 是治疗 ALI 的一种有前途的药物。