Wang Wenjun, Li Qijuan, Yan Xiaomin, Chen Ziqiang, Xie Yu, Hu Huiling, Wang Zhanguo
Key Laboratory of Standardization of Chinese Herbal Medicine, Ministry of Education, State Key Laboratory Breeding Base of Characteristic Chinese Medicine resources in Southwest China, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Key Laboratory of Standardization of Chinese Herbal Medicine, Ministry of Education, State Key Laboratory Breeding Base of Characteristic Chinese Medicine resources in Southwest China, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Phytomedicine. 2020 Apr 27;70:153224. doi: 10.1016/j.phymed.2020.153224.
Vladimiriae Radix (VR) is the dry root of Vladimiria souliei (Franch.) Ling or Vladimiria souliei (Franch.) Ling var. cinerea Ling. Costunolide (CO) and dehydrocostus lactone (DE) are the two most effective active ingredients of VR. Raw Vladimiriae radix (rVR) and processed Vladimiriae radix (pVR) are the two most common forms. They have been used for hundreds of years to treat gastritis, gastric ulcer and gastrointestinal pain, but their protective effects on gastric mucosa have been widely considered to be different, and the mechanism is not clear.
A comparative study of in vivo process and efficacy difference of raw and processed Vladimiriae Radix was carried out to explore the treatment mechanism and to provide reference for the rationality of clinical usage.
In this study, multi-batch rVR and pVR were used to establish the characteristic chromatograms through high performance liquid chromatography (HPLC) to control the qualities of their extracts. A rapid and accurate ultra-high performance liquid chromatography - mass spectrometry (UPLC-MS) method was established and verified, and the concentrations of CO and DE in plasma of rats after oral administration were determined to analyze the pharmacokinetics. The anti-inflammatory and antioxidant activities of ethanol-induced acute gastric mucosa injury (AGMI) in rats were quantitatively analyzed by ELISA and Westernblot methods.
Characteristic chromatograms study showed that there were 9 common characteristic peaks between the chromatograms of rVR and pVR, and there was a high level (> 0.90) of the similarity between batches (only one batch less than 0.90). The increased levels of T, T and MRT were found in rats treated with the pVR. Animal model studies indicated that both the two forms of VR could relieve AGMI, but pVR could more effectively reduce the content of ethanol in blood and lower the levels of TNF-α, IL-6, IL-1β, NO, iNOS and MDA, and increase the level of SOD. Results of Westernblot proved that pVR also could inhibit the expression of NF-κB p65, IκBα and up-regulate the expression of HO-1 and NRF2 more operatively to protect gastric mucosa through anti-inflammatory and antioxidant stress mechanisms.
Compared with rVR, pVR has an accelerated absorption in vivo and its effect time was prolonged, and the observed improvement of anti-AGMI effect was achieved through anti-oxidation and anti-inflammation regulation.
川木香是川木香（Vladimiria souliei (Franch.) Ling）或灰毛川木香（Vladimiria souliei (Franch.) Ling var. cinerea Ling）的干燥根。木香烃内酯（CO）和去氢木香内酯（DE）是川木香两种最有效的活性成分。生川木香（rVR）和制川木香（pVR）是两种最常见的形式。它们已被用于治疗胃炎、胃溃疡和胃肠道疼痛数百年，但它们对胃黏膜的保护作用被广泛认为有所不同，且机制尚不清楚。
对生、制川木香的体内过程和药效差异进行比较研究，以探讨其治疗机制，为临床合理用药提供参考。
本研究采用多批次的rVR和pVR，通过高效液相色谱法（HPLC）建立特征图谱以控制其提取物质量。建立并验证了一种快速准确的超高效液相色谱 - 质谱联用（UPLC-MS）方法，测定大鼠口服给药后血浆中CO和DE的浓度以分析药代动力学。采用ELISA和Westernblot方法对乙醇诱导的大鼠急性胃黏膜损伤（AGMI）的抗炎和抗氧化活性进行定量分析。
特征图谱研究表明，rVR和pVR的色谱图之间有9个共同特征峰，批次间相似度较高（> 0.90）（仅一批低于0.90）。用pVR处理的大鼠中发现T、T和MRT水平升高。动物模型研究表明，两种形式的川木香均可缓解AGMI，但pVR能更有效地降低血液中乙醇含量，降低TNF-α、IL-6、IL-1β、NO、iNOS和MDA水平，并提高SOD水平。Westernblot结果证明，pVR还可更有效地抑制NF-κB p65、IκBα的表达，并上调HO-1和NRF2的表达，通过抗炎和抗氧化应激机制保护胃黏膜。
与rVR相比，pVR在体内吸收加快，作用时间延长，其抗AGMI作用的改善是通过抗氧化和抗炎调节实现的。
