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JOURNAL OF ETHNOPHARMACOLOGY · 2022 · IF 5.195

Study on the mechanism of reducing biofilm toxicity and increasing antioxidant activity in vinegar processing phytomedicines containing pentacyclic triterpenoid saponins

Tingting Wang,Yonggui Song,Huanhua Xu,Yali Liu,Hongwei He,Mingyue Zhou,Chen Jin,Ming Yang,Zhifu Ai,Dan Su

Ethnopharmacological relevance Pentacyclic triterpenoid saponin (PTS) is a kind of particular chemicals with various pharmacological activities, as well as surface activity, mucosal irritation and hemolysis. PTS is closely related to the exertion of efficacy or adverse reactions in plant medicines rich in this component. For the better clinical application of natural resources, how to reduce toxicity and enhance curative efficacy is an important problem which needs to be solved at present. Till now, there has been few studies directly investigating the problem. Aim of study Through comparison study of Radix Bupleuri (Chai hu) and Pulsatilla chinensis (Bai tou weng), which are typical traditional Chinese medicines containing PTS, explore the potential change rule of material basis and the mechanism of detoxification and synergistic effect of vinegar processing. Materials and methods Composition change rule after vinegar processing was applied by UPLC-QTOF-MS/MS coupled with principal component analysis (PCA). Based on our previous research, this paper expounded the action mechanism from the perspective of reducing biofilm toxicity and increasing antioxidant activity. Direct toxicity reducing information was obtained at the cellular level including cellular morphology, MTT assays, western blots and RT-PCR in L02 cells with overload sphingomyelin (SM). The synergistic effect was investigated through histological examinations, mesenteric hemorheology, ELISA, flow cytometry and confocal microscopy. Results It was found that the structure of PTS take place a series of chemical reactions in the process of vinegar processing which enabled the more toxic components transformed into less toxic components and components with clear efficacy, so as to achieve the purpose of detoxification and synergistic effect. The results indicated that the mechanism of detoxification in vinegar processing was that vinegar processing could act on SM, cause less balance disturbance to sphingomyelin/ceramide (SM/Cer), inhibit apoptosis and then alleviate toxicity. In addition, the pharmacodynamic results showed that the vinegar processing could have an obvious synergistic effect through anti-oxidant stress. Conclusions By changing the structures of the PTS, the SM/Cer disrupt was reduced and the antioxidant activity was enhanced, so as to decrease toxicity and increase efficiency in vinegar processing phytomedicines containing PTS.

CAS / MDL: 7440-19-9
研究领域: 民族药理学 · 药理学 · 中药学 · 化学 · 毒理学
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JOURNAL OF PHARMACY AND PHARMACOLOGY · 2014 ·Vol. 66 ·期 10 ·1410-1420 · IF 2.161

Improvement of pulmonary absorptions of poorly absorbable drugs using Gelucire 44/14 as an absorption enhancer

Zhang Hailong,Huang Xiaoyan,Mi Jie,Huo Yayu,Wang Guan,Xing Jianfeng,Gao Yang

ObjectivesThis study aims to evaluate the absorption-enhancing effects of Gelucire 44/14 on the pulmonary absorption of different poorly absorbable drugs and relative mechanism of action.MethodsAbsorption-enhancing effect of Gelucire 44/14 were examined by an in-vivo pulmonary absorption experiment in rats, and the membrane toxicity of Gelucire 44/14 was evaluated by measuring levels of protein and dehydrogenase (LDH) in the bronchoalveolar lavage fluid (BALF) and morphological observation.Key findingsPulmonary absorptions of fluorescein isothiocyanate-dextrans, insulin and calcitonin were enhanced by Gelucire 44/14 (0.1–2.0%, w/v) in a concentration-dependent manner, and the maximal absorption-enhancing effect was obtained when the concentration of Gelucire 44/14 increased to 2.0% (w/v). Furthermore, Gelucire 44/14 neither increase the levels of protein and LDH in BALF nor change morphology of lung compared with control group. In addition, a well correlation between the absorption-enhancing effect and surface tension of insulin solution in the presence of Gelucire 44/14 was observed, suggesting Gelucire 44/14-mediated decrease in the surface tension of the gas-liquid interface in alveolar tissue was possible one of the improving mechanisms of Gelucire 44/14.ConclusionGelucire 44/14 was a potential and safe absorption enhancer for improving the absorption of poorly absorbable drugs including insulin and calcitonin by pulmonary delivery.

CAS / MDL: 47931-85-1
研究领域: 药剂学 · 药理学 · 药物递送系统
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