Therapeutic potential of Gymnema sylvestre on diverse cell types is predominantly due to a variety of terpenoids and their derivatives. However, their bioavailability becomes limited due to poor solubility and lower lipophilic properties, provoking the search for novel membranotropic terpenoids and their mechanism of action. A terpenoid fraction purified from Gymnema sylvestre exhibited broad spectrum antimicrobial activity against both Gram positive and Gram negative bacteria with IC₅₀ ˂ 0.1 mg/ml. Evaluation of its membranotropic effect in vitro on reconstituted model membrane revealed that the fraction induced flip-flop of fluorescent phospholipid analogs across the lipid bilayer. The terpenoid-induced lipid flipping was biphasic with a fast linear phase (rate constant (k₁) = 3 to 5 S⁻¹) and a second slow exponential phase (rate constant (k₂) = (4 to 9) × 10⁻³ S⁻¹). The lipid-flippase activity of the terpenoid fraction showed concentration and incubation-dependent cooperativity, indicating their lipophilic nature and membrane-destabilizing activity that facilitated lipid translocation. For the first time, our study reveals the flippase activity of a terpenoid fraction of Gymnema sylvestre that could be further explored for their membrane-mediated pharmacological properties.

Graphical Abstract

Gymnema sylvestre对不同细胞类型的治疗潜力主要是由于各种萜类化合物及其衍生物。然而，由于溶解性差和亲脂性较低，它们的生物利用度受到限制，这引发了对新型膜性萜类化合物及其作用机制的研究。从匙羹藤中纯化的萜类成分对革兰氏阳性菌和革兰氏阴性菌均表现出广谱抗菌活性，IC ₅₀˂ 0.1 毫克/毫升。对其体外对重建模型膜的亲膜效应的评估表明，该分数诱导了跨脂质双层的荧光磷脂类似物的触发器。萜类诱导的脂质翻转是双相的，具有快速线性阶段（速率常数 ( k ₁ ) = 3 至 5 S ^-1）和第二个缓慢指数阶段（速率常数 ( k ₂ ) = (4 至 9) × 10 ^{-） 3}  S ^-1）。萜类成分的脂质翻转酶活性显示出浓度和孵化依赖性协同性，表明它们的亲脂性和促进脂质易位的膜去稳定活性。我们的研究首次揭示了匙羹藤萜类成分的翻转酶活性，可以进一步探索其膜介导的药理特性。

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