一种预防木香和土木香致胆汁淤积性肝损伤的有效方法：抑制炎症反应和调节胆汁酸受体的表达。

An effective method for preventing cholestatic liver injury of Aucklandiae Radix and Vladimiriae Radix: Inflammation suppression and regulate the expression of bile acid receptors.

机构信息

State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.

出版信息

J Ethnopharmacol. 2022 Aug 10;294:115330. doi: 10.1016/j.jep.2022.115330. Epub 2022 Apr 29.

DOI:10.1016/j.jep.2022.115330

PMID:35500801

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Aucklandiae Radix (AR) and Vladimiriae Radix (VR) were used to treat gastrointestinal, liver and gallbladder diseases at practice. In most conditions, VR was used to be a substitute of AR or a local habit may attribute to the same main active ingredients Costunolide and Dehydrocostus lactone, which presented many similar pharmacological activities. However, other different lactone compounds in AR and VR also play a role in disease treatment, so the difference in therapeutic effects of AR and VR in related diseases needs to be further studied.

AIMS OF THE STUDY

Revealing the differences between the chemical compounds of the total lactone extracts of AR and VR (TLE of AR and VR) and the differences in the protective effects of cholestatic liver injury to ensure rational use of AR and VR.

STUDY DESIGN AND METHODS

The macroporous adsorption resin was used to purify and enrich the lactone compounds to obtain the total lactone extracts of AR and VR. HPLC-PDA was used to obtain the data to establish chemical fingerprint and chemometric analysis to compare similarities and differences between TLE of AR and VR. The pharmacodynamic experiment revealed how TLE of AR and VR to show protect effects on cholestatic liver injury.

RESULTS

Similarity analysis results showed TLE of AR and VR had a high similarity (>0.9). Nevertheless, difference analysis results showed 4 compounds, Costunolide, Dehydrocostus lactone, 3β-acetoxy-11β-guaia-4 (15), 10 (14)-diene-12,6α-olide and vladinol F may contribute to the differences between them. The pharmacodynamics experiments results showed the TLE of AR and VR affected the different liver cholate-associated transporters mRNA expression (TLE of AR up-regulated CYP7A1, TLE of VR down-regulated FXR and BSEP), the TLE of AR and VR had an effect to regulate biochemical indicators (AST, ALT, ALP, TBA) of liver function, and TLE of VR was better than TLE of AR in reducing the expression of inflammatory factors (IL-6 and IL-1β).

CONCLUSION

The liver protection of AR and VR have been confirmed, but the differences of material basis and mechanism of drug efficacy needed further study to guarantee formulation research and provide theoretical references for clinical rational applications of AR and VR.

摘要

民族药理学相关性

在实践中，莪术和土木香被用于治疗胃肠道、肝脏和胆囊疾病。在大多数情况下，土木香被用作莪术的替代品，或者可能是由于相同的主要活性成分——木香烃内酯和去氢木香内酯，它们具有许多相似的药理活性。然而，莪术和土木香中其他不同的内酯化合物也在疾病治疗中发挥作用，因此莪术和土木香在相关疾病中的治疗效果差异需要进一步研究。

研究目的

揭示莪术和土木香总内酯提取物（AR 和 VR 的 TLE）的化合物差异，以及对胆汁淤积性肝损伤的保护作用差异，以确保莪术和土木香的合理使用。

研究设计与方法

采用大孔吸附树脂对内酯化合物进行纯化和富集，得到莪术和土木香的总内酯提取物。采用高效液相色谱-光电二极管阵列法（HPLC-PDA）获得数据，建立化学指纹图谱，并进行化学计量学分析，比较 AR 和 VR 的 TLE 之间的相似性和差异性。药效学实验揭示了 AR 和 VR 的 TLE 如何对胆汁淤积性肝损伤发挥保护作用。

结果

相似性分析结果表明，AR 和 VR 的 TLE 具有高度相似性（>0.9）。然而，差异分析结果表明，4 种化合物——木香烃内酯、去氢木香内酯、3β-乙酰氧基-11β-愈创木-4（15），10（14）-二烯-12，6α-内酯和土木香 F，可能是导致它们之间差异的原因。药效学实验结果表明，AR 和 VR 的 TLE 影响不同的肝胆汁相关转运体 mRNA 表达（AR 的 TLE 上调 CYP7A1，VR 的 TLE 下调 FXR 和 BSEP），AR 和 VR 的 TLE 对肝功能生化指标（AST、ALT、ALP、TBA）有调节作用，VR 的 TLE 在降低炎症因子（IL-6 和 IL-1β）表达方面优于 AR 的 TLE。