Abstract

BackgroundVladimiriae 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. PurposeA 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. MethodsIn 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. ResultsCharacteristic 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 Tmax, T1/2 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. ConclusionCompared 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.

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