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<p>The internalization and accumulation of calcium crystals (crystallopathy) trigger the overproduction of reactive oxygen species (ROS), which drive localized tubular injury and subsequently dysregulate Ca²⁺ signaling, leading to chronic kidney disease (CKD). Here, we investigated the protective mechanism of aqueous <i>Ocimum sanctum</i> (Krishna Tulsi) leaf extract, often used to prepare as Tulsi Chai (TC), for its effects on cell survival, wound healing, and Ca²⁺ signaling in human kidney-2 (HK-2) cells. We induced oxidative stress with hydrogen peroxide (H₂O₂) and simulated CKD-like injury with calcium phosphate (CaP) crystals. TC pretreatment significantly reduced intracellular ROS production and improved cell viability in a dose-dependent manner, indicating a protective role for TC. Moreover, a scratch-wound model showed that the rate of wound closure was directly proportional to the dose of TC exposure, underscoring its role in epithelial migration during wound healing. CaP-induced apoptosis and necrosis were markedly decreased in HK-2 cells when pretreated with TC, suggesting its utility in alleviating crystallopathy, as a CKD-like conditions. Interestingly, TC ameliorated the rise in CaP-induced store-operated Ca²⁺-signaling (SOCE) dynamics during wound healing process using HK-2 cells, indicating TC’s ability to normalize the SOCE signature towards minimizing CKD-like pathogenic conditions. More importantly, TC attenuated CaP-induced wound closure through phosphorylation of p38 mitogen-activated protein kinase. Altogether, TC’s ability to remediate both ROS-induced injury and tubular crystallopathy in HK-2 cells support its further advancement towards preclinical evaluation in animal models, determining its potential as a natural regenerative substance for promoting the process of wound healing under CKD-like conditions.</p>

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Modulation of Ca2+ signaling by tulsi (holy basil) extract in renal epithelial wound-healing model

  • 期刊论文

  • 发表日期：

    2026年7月15日

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  • Onyebuchi C. Ukaeje,
  • Samuel Shin,
  • Bidhan C. Bandyopadhyay

摘要

The internalization and accumulation of calcium crystals (crystallopathy) trigger the overproduction of reactive oxygen species (ROS), which drive localized tubular injury and subsequently dysregulate Ca²⁺ signaling, leading to chronic kidney disease (CKD). Here, we investigated the protective mechanism of aqueous Ocimum sanctum (Krishna Tulsi) leaf extract, often used to prepare as Tulsi Chai (TC), for its effects on cell survival, wound healing, and Ca²⁺ signaling in human kidney-2 (HK-2) cells. We induced oxidative stress with hydrogen peroxide (H₂O₂) and simulated CKD-like injury with calcium phosphate (CaP) crystals. TC pretreatment significantly reduced intracellular ROS production and improved cell viability in a dose-dependent manner, indicating a protective role for TC. Moreover, a scratch-wound model showed that the rate of wound closure was directly proportional to the dose of TC exposure, underscoring its role in epithelial migration during wound healing. CaP-induced apoptosis and necrosis were markedly decreased in HK-2 cells when pretreated with TC, suggesting its utility in alleviating crystallopathy, as a CKD-like conditions. Interestingly, TC ameliorated the rise in CaP-induced store-operated Ca²⁺-signaling (SOCE) dynamics during wound healing process using HK-2 cells, indicating TC’s ability to normalize the SOCE signature towards minimizing CKD-like pathogenic conditions. More importantly, TC attenuated CaP-induced wound closure through phosphorylation of p38 mitogen-activated protein kinase. Altogether, TC’s ability to remediate both ROS-induced injury and tubular crystallopathy in HK-2 cells support its further advancement towards preclinical evaluation in animal models, determining its potential as a natural regenerative substance for promoting the process of wound healing under CKD-like conditions.