Evaluation of the bioavailability of major withanolides of Withania somnifera using an in vitro absorption model system.
Evaluation of the bioavailability of major withanolides of Withania somnifera using an in vitro absorption model system.
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DOI：
10.4103/2231-4040.165023
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发表时间：
2015-10
影响因子：
1.4
通讯作者：
Hegde MV
中科院分区：
文献类型：
--
作者：
Devkar ST;Kandhare AD;Sloley BD;Jagtap SD;Lin J;Tam YK;Katyare SS;Bodhankar SL;Hegde MV
Withania somnifera (L.) Dunal，显示出多种药理学特性，这些特性主要归因于根中存在的睡茄内酯。药用活性茄内酯成分的功效取决于通过肠上皮的吸收和运输。我们通过采用Sino-Veda Madin-Darby犬肾细胞培养系统检查了这些特性，该系统在体外条件下显示出与人肠上皮相似的吸收特性。因此，本研究的目的是评估单个茄内酯的生物利用度。将睡茄内酯以 2 μg/ml 的浓度稀释在 Hank's 缓冲盐水中，并进行持续 1 小时的渗透性研究。渗透率是根据流出泵 (Peff) 测量的，单位为 cm/s。睡茄内酯 A (WN A)、睡茄酮 (WNN)、1,2-脱氧睡茄内酯 (1,2 DWM)、睡茄内酯 B (WNB)、睡茄内酯 IV-V (WS IV-V) 和睡茄素 A 的 Peff 值为 4.05 × 10−5、2.06 × 10−5、1.97 × 10−5、1.80 ×分别为 10−5、3.19 × 10−6、3.03 × 10−6 和 3.30 × 10−7。总之，非极性低分子量化合物（WNA、WNN、1,2 DWM 和 WNB）具有高渗透性。与此相反，糖基化和极性的 WS IV 和 WS V 显示出低渗透性。令人惊讶且矛盾的是，具有高度生物活性的醉茄素 A 是完全不可渗透的，这表明可能需要使用人上皮结直肠腺癌细胞 (Caco-2) 细胞进行进一步研究，以描绘醉茄内酯，尤其是醉茄素 A 的吸收特性。
Withania somnifera (L.) Dunal, shows several pharmacological properties which are attributed mainly to the withanolides present in the root. The efficacy of medicinally active withanolides constituents depends on the absorption and transportation through the intestinal epithelium. We examined these characteristics by employing the Sino-Veda Madin-Darby canine kidney cells culture system, which under in vitro condition shows the absorption characteristics similar to the human intestinal epithelium. Thus, the aim of the present investigation was to assess the bioavailability of individual withanolides. Withanolides were diluted in Hank's buffered saline at a concentration of 2 μg/ml were tested for permeability studies carried out for 1 h duration. Permeability was measured in terms of efflux pump (Peff) in cm/s. Peff values of withanolide A (WN A), withanone (WNN), 1,2-deoxywithastramonolide (1,2 DWM), withanolide B (WN B), withanoside IV-V (WS IV-V), and withaferin A were 4.05 × 10−5, 2.06 × 10−5, 1.97 × 10−5, 1.80 × 10−5, 3.19 × 10−6, 3.03 × 10−6 and 3.30 × 10−7 respectively. In conclusion, the nonpolar and low molecular weight compounds (WN A, WNN, 1,2 DWM, and WN B) were highly permeable. As against this, the glycosylated and polar WS IV and WS V showed low permeability. Surprisingly and paradoxically, the highly biologically active withaferin A was completely impermeable, suggesting that further studies possibly using human epithelial colorectal adenocarcinoma (Caco-2) cells may be needed to delineate the absorption characteristics of withanolides, especially withaferin A.