Department of Medicinal Natural Products, West China School of Pharmacy, Sichuan University, No.17, Section 3, Renmin Nan Road, Chengdu, Sichuan Province, 610041, PR China.
Nin Jiom Medicine Manufactory (H.K.) Limited, Hongkong, China.
J Ethnopharmacol. 2019 Jun 28;238:111853. doi: 10.1016/j.jep.2019.111853. Epub 2019 Apr 4.
Fritillariae Bulbus ("Beimu" in Chinese) is a famous traditional Chinese medicine used to treat cough, expectoration and asthma for more than 2000 years, which belongs to the Fritillaria genus in Liliaceae family. Bulbs of Fritillaria cirrhosa D.Don (BFC) and bulbs of Fritillaria pallidiflora Schrenk (BFP) are two important drugs of Beimu. Due to the significant similarities in their outward appearance characters and chemical profiles, BFC has often been adulterated with BFP in Chinese Traditional Medicine markets.
This study aims to compare the oral acute toxicity and the traditional pharmacological activities including antitussive, expectorant and anti-inflammatory effects between the extract of BFC and BFP, to clear and definite if the BFP can be used as a substitute of the BFC in the application of traditional medicine.
The extracts were prepared through refluxing with 80% ethanol solvent. For the acute toxicity tests, graded doses of BFP extracts and the maximum dose of BFC extracts were administered orally to mice. The animals were observed for toxic symptoms and mortality daily for 14 days. For the pharmacological activities tests, graded doses of BFP and BFC extracts were administered orally to mice. To observe the effects relieving cough, expelling phlegm and lessening the ear swelling of BFC extracts and BFP extracts through ammonia liquor inducing cough, phenol red apophlegmating in mice and the xylene-induced auricular swelling of mouse, respectively.
In the acute toxicity study, the LD value of BFP in mice was calculated to be 213.57 g/kg body weight, and the maximum feasible dose (MFD) value of BFC in mice was 452.14 g/kg. Histopathological analysis has shown inflammatory cells infiltration and cells edema in liver, multinucleated giant cell proliferation in spleen, perivascular exudate and hemorrhage in lung, glomerulus atrophy in kidney of mice after oral administrations of BFP extracts. But only liver cells edema was observed in BFC group. Both BFC extract and BFP extract significantly increased latent period of cough and inhibited cough frequency in mice induced by ammonia. Besides, the two extracts also obviously enhanced mice's tracheal phenol red output in expectorant assessment and inhibited the development of ear edema in anti-inflammatory evaluation assay.
To summarize, the BFP has the significant similarities in morphological characteristics, chemical profiles and traditional pharmacological activities compared with the BFC. The result of this study provide some valid scientific support for using BFP as a plant substitute of the BFC, but considering the toxicity of BFP is much higher than BFC, we don't recommend long-term oral administration of BFP or exceeding recommended dosage of Chinese Pharmacopoeia 2015.
贝母（“北母”在中国）是一种著名的中药，用于治疗咳嗽、咳痰和哮喘已有 2000 多年的历史，属于百合科贝母属。浙贝母（BFC）和伊犁贝母（BFP）的鳞茎是北母的两种重要药物。由于它们的外观特征和化学成分非常相似，BFC 在中国传统医药市场上经常与 BFP 混合。
本研究旨在比较 BFC 和 BFP 提取物的口服急性毒性和传统药理活性，包括镇咳、祛痰和抗炎作用，以明确 BFP 是否可以替代 BFC 在传统医学中的应用。
提取物通过 80%乙醇溶剂回流制备。对于急性毒性试验，给予 BFP 提取物的分级剂量和 BFC 提取物的最大剂量口服给予小鼠。每天观察动物 14 天，观察毒性症状和死亡率。对于药理活性试验，给予 BFP 和 BFC 提取物的分级剂量口服给予小鼠。通过氨诱导咳嗽、酚红祛痰和二甲苯诱导小鼠耳肿胀，分别观察 BFC 提取物和 BFP 提取物对咳嗽、祛痰和减轻耳肿胀的影响。
在急性毒性研究中，计算出 BFP 在小鼠中的 LD 值为 213.57g/kg 体重，BFC 在小鼠中的最大可行剂量（MFD）值为 452.14g/kg。组织病理学分析显示，BFP 提取物口服给药后，小鼠肝脏出现炎症细胞浸润和细胞水肿，脾脏出现多核巨细胞增殖，肺血管周围渗出和出血，肾脏出现肾小球萎缩。但 BFC 组仅观察到肝细胞水肿。BFC 提取物和 BFP 提取物均显著延长了氨诱导的小鼠咳嗽潜伏期，抑制了咳嗽频率。此外，两种提取物还明显增强了小鼠的气管酚红排出量，在祛痰评价中抑制了耳肿胀的发展，并在抗炎评价中抑制了耳肿胀的发展。
综上所述，BFP 在形态特征、化学特征和传统药理活性方面与 BFC 有显著的相似性。本研究结果为 BFP 作为 BFC 的植物替代品提供了一些有效的科学依据，但考虑到 BFP 的毒性比 BFC 高得多，我们不建议长期口服 BFP 或超过 2015 年版《中国药典》推荐剂量。
