Putri Cahaya Situmorang, Helen Helen, Syafruddin Ilyas, Pandu Surya Pangestu, Syahputra Wibowo, Kaniwa Berliani, Alexander Patera Nugraha, Khatarina Meldawati Pasaribu
The increasing use of herbal electronic cigarettes raises concerns regarding their biological impact beyond conventional nicotine delivery. Although marketed as “natural” alternatives, their phytochemical vapors interact with molecular pathways that may influence respiratory health. This review summarizes current evidence on the molecular crosstalk between herbal phytochemicals and microRNAs (miRNAs) in the context of electronic cigarette vapor exposure, emphasizing their roles in oxidative stress, inflammation, and tissue remodelling. Literature was systematically examined to evaluate in vitro, in vivo, and bioinformatics findings on phytochemicals commonly incorporated in herbal e-liquids. Key molecular pathways (NF-κB, Nrf2/HO-1, MAPK, PI3K/Akt/mTOR, and TGF-β/Smad) and miRNA regulators were analyzed to elucidate mechanisms of lung injury and protection. The search strategy involved PubMed, Web of Science, and Scopus databases, using the keywords “herbal e-liquid,” “phytochemicals,” “lung injury,” “miRNA,” and “molecular pathway.” Evidence indicates that bioactive phytochemicals such as quercetin, linalool, and EGCG can modulate the expression of miRNAs (e.g., miR-21, miR-146a, miR-155, miR-210), thereby regulating inflammatory and oxidative responses. Crosstalk between these phytochemicals and miRNAs contributes to dual effects: mitigating reactive oxygen species and cytokine overproduction, while in some cases promoting pro-inflammatory or fibrotic signalling under chronic exposure. This bidirectional modulation highlights the complex balance between potential therapeutic benefits and risks of herbal vapor inhalation. Herbal electronic cigarettes cannot be considered risk-free. Their phytochemicals engage in intricate interactions with miRNA networks and molecular pathways that may influence respiratory health. Understanding this molecular crosstalk is essential for evaluating safety, guiding regulatory strategies, and identifying therapeutic prospects of phytochemical-based inhalation systems. © 2026 Elsevier B.V.
Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Sumatera Utara, Medan, Indonesia; Department of Pharmacology, Faculty of Pharmacy, Universitas Sumatera Utara, Medan, Indonesia; Department of Social anthropology, Faculty of Social Sciences, Universitas Negeri Medan, Medan, Indonesia; Eijkman Research Center for Molecular Biology, National Research and Innovation Agency (BRIN), Bogor, 16911, Indonesia; Department of Orthodontic, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia; Research Center for Biomass and Bioproducts, National Research and Innovation Agency of Indonesia (BRIN), Cibinong, 16911, Indonesia
