ROS and reactive nitrogen species (RNS) are highly reactive molecules that are capable of inducing cellular damage through lipid peroxidation, protein oxidation, and DNA modification. Oxidative stress occurs when there is an imbalance between the oxidant generation and the antioxidant defense systems, thus leading to dysfunction of biological systems [17]. TQ has been shown to regulate cellular redox homeostasis in a concentration and cell type dependent manner.

In BEAS-2B cells exposed to cigarette smoke extracts, the treatment with TQ at concentrations of 20 and 50 µM significantly increased the activities of antioxidant enzymes, including SOD, CAT, and GSH reductase (GR), in parallel with elevated intracellular GSH levels [18]. In contrast, in cancer cells, TQ molecule exerts a pro-oxidant effects that contribute to its anticancer activity. For example, in A549 lung cancer cells, the exposure to TQ (20–60 µM) resulted in an increased total oxidant status (TOS) and decreased total antioxidant capacity (TAC), along with the reduced activities of antioxidant enzymes such as SOD, CAT, and GSH peroxidase, therefore promoting oxidative stress selectively in malignant cells [19].

In vivo studies further support the antioxidant potential of TQ. In a bleomycin-induced pulmonary fibrosis rat model, oral administration of TQ (10 and 20 mg/kg for 28 days) significantly decreased the oxidative and inflammatory damage by increasing GSH and SOD levels while reducing malondialdehyde (MDA) concentrations. These effects were mediated through activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway and suppression of the nuclear factor-kappa B (NF-κB) expression [20]. Additionally, TQ has been reported to inhibit cyclooxygenase-2 (COX-2) expression and prostaglandin production in models of allergic airway inflammation, further supporting its role in the redox and inflammatory regulation [21].

The molecular mechanism of TQ for protecting cells against oxidative damage is summarized in Figure 1.

HO-1 is a cytoprotective enzyme that is involved in heme degradation and plays a key role in protecting tissues against oxidative stress, inflammation, and carcinogenesis. The expression of HO-1 is mainly regulated by the redox-sensitive transcription factor Nrf2, which binds to antioxidant response element (ARE) in the promoter regions of target genes. In normal conditions, Nrf2 is sequestered in the cytoplasm by Kelch-like ECH-associated protein 1 (Keap1), leading to its proteasomal degradation. Upon oxidative stress, the Nrf2 dissociates from Keap1, translocates to the nucleus, and initiates transcription of antioxidant genes.

Experimental evidence shows that the TQ molecule activates the Nrf2/HO-1 pathway. Cells treated with TQ (1–20 µM) for six hours showed significant induction of HO-1 expression at both mRNA and protein levels through Nrf2 activation [22, 23]. Moreover, TQ induced Nrf2 signaling was associated with downregulation of pro-inflammatory cytokines such as interleukin-1β (IL-1β), showing its dual role as antioxidant and anti-inflammatory [24].

The molecular mechanism of TQ for the regulation of Nrf2/HO-1 signaling pathway is summarized in Figure 2.

TQ exhibits a major anti-inflammatory activity by regulating multiple inflammatory mediators and signaling pathways. Several cytokine profiling studies demonstrated that TQ suppresses the tumor necrosis factor-α (TNF-α) as well as other pro-inflammatory cytokines. In TNF-α-stimulated synovial fibroblasts, TQ treatment (0–1 µM) significantly reduced nitric oxide (NO), IL-6, IL-8, and prostaglandin E₂ (PGE₂) production in a concentration-dependent manner. These effects were associated with inhibition of Akt phosphorylation, indicating its crosstalk with other intracellular inflammatory signaling pathways [25].

The in vivo studies further confirmed the protective role of TQ against inflammation induced tissue damage. For example, in cisplatin-induced testicular toxicity, TQ decreased the tissue injury by regulating the TNF-α/OTULIN/NF-κB signaling pathway [26]. In a lipopolysaccharide (LPS)-induced neuroinflammation rat model, by using the Evans blue dye method, TQ significantly reduced the blood brain barrier permeability and improved the behavioral performance. These findings indicate that TQ preserves blood brain barrier integrity and reduces inflammation associated with behavioral impairments [27].

TQ has demonstrated marked anticancer activity through regulation of apoptosis, cell survival pathways, and cytoskeletal properties. For example, in breast cancer cells, TQ upregulated peroxisome proliferator-activated receptor γ (PPAR-γ) while downregulating anti-apoptotic genes such as Bcl-2 and Bcl-xL, thus inducing programmed cell death. Molecular docking studies have revealed the interactions between TQ and both polar and non-polar residues within the PPAR-γ binding site, supporting its direct modulatory role [15].

Lipid peroxidation products can form adducts with proteins and DNA, contributing to the progression of tumor. The inhibitory effect of TQ on lipid peroxidation has therefore been proposed as one mechanism underlying its cytoprotective and anticancer effects [21]. Moreover, TQ had inhibited the migration of metastatic human (A375) and murine (B16F10) melanoma cells by suppressing NLRP3 inflammasome activation and reducing caspase-1 cleavage [28].

At the cytoskeletal level, TQ targeted α/β-tubulin proteins in cancer cells, inducing their degradation through the upregulation of the tumor suppressor p73 and activation of caspase dependent apoptosis. Importantly, there were no significant effects observed in normal human fibroblasts. However, in glioblastoma cells, TQ induced apoptosis while inhibiting autophagy, thereby enhancing the anticancer efficacy [28]. Furthermore, in acute lymphoblastic leukemia (CEMss) cells, Treatment of CEMss cells with TQ exhibited strong antiproliferative activity (IC₅₀ = 1.5 µg/mL) by downregulating Bcl-2 and upregulating Bax, leading to apoptosis and inhibition of growth [29].

The molecular mechanism of TQ in controlling cellular apoptosis for normal cells is summarized in Figure 3.

TQ has also demonstrated a notable antiviral activity in both in vivo and in vitro models. In a murine cytomegalovirus infection model, TQ significantly reduced viral loads in the liver and spleen, which is accompanied by enhanced interferon-γ production and increased CD4⁺ T-cell responses [30]. In vitro studies have reported a significant antiviral activity of TQ against a SARS-CoV-2 strain isolated from Egyptian patients [31]. Also, TQ was also shown to inhibit Epstein-Barr virus replication in infected B cells and reduce the replication of certain coronaviruses [32, 33].

In addition, TQ exhibits broad antimicrobial activity against several pathogenic bacteria, including Streptococcus constellatus, Streptococcus mutans, Gemella haemolysans, and Streptococcus mitis, with inhibition of bacterial biofilm formation. Antibacterial effects have also been observed against Staphylococcus aureus, Salmonella enteritidis, Salmonella typhimurium, Shigella flexneri, Pseudomonas aeruginosa, and Escherichia coli [15]. TQ has further been proposed as a potential agent for controlling the spore forming bacteria such as Alicyclobacillus acidoterrestris.

Regarding the antifungal and the antiparasitic activities, TQ demonstrated potent antifungal effects against eight dermatophyte species, showing greater efficacy than griseofulvin. Additionally, TQ exhibited strong antiparasitic activity against Giardia lamblia and Entamoeba histolytica [34, 35].

The ability of TQ to regulate oxidative stress, inflammation, and cell survival pathways, TQ has been extensively studied for its therapeutic potential in neurodegenerative disorders, especially AD.

Following ischemic events, neuronal death is primarily driven by the oxygen and glucose deprivation, which triggers oxidative stress, acidosis, and glutamate-mediated cytotoxicity [42]. Oxidative stress is considered a central contributor to the neuronal injury in neurodegenerative conditions, making it a key target for neuroprotective interventions. TQ molecule exhibits neuroprotective effects largely by its potent antioxidant activity, reducing both acute and chronic cerebral pathologies by restoring antioxidant enzyme levels and preventing excessive lipid peroxidation [43].

In AD, oxidative stress plays a major role in the disease progression. Experimental models of transient cerebral ischemia have shown that the daily administration of TQ enhances neuronal survival in the hippocampal CA1 region, which preserves normal levels of GSH, SOD, and CAT, and reduces MDA concentrations in the brain tissues. These protective effects are mediated by TQ-induced activation of the Nrf2 and HO-1 pathway [41].

Further animal studies highlight that TQ has potential against the chemically induced neurotoxicity. For example, intraperitoneal administration of aluminum chloride (AlCl₃, 10 mg/kg for 6 weeks) caused impaired motor coordination, anxiety, depression, increased MDA levels, and reduced overall antioxidant capacity. But daily treatment with TQ (10 mg/kg, intraperitoneally) effectively reversed these effects [44]. Additionally, in a scopolamine-induced AD model, rats treated with TQ (20 mg/kg, intraperitoneally, 1 h before scopolamine 1 mg/kg) showed reduction in the brain lipid peroxidation, which supports the role of TQ as a potential adjunctive therapy for AD [45].

Neuroinflammation is the central driver of neurodegenerative processes, which include AD. The activation of microglia is a key event in initiating and maintaining such an inflammatory response, triggered by several stimulations such as infections or traumatic brain injury (TBI). The activated microglia stimulate the NF-κB, which in turn upregulates many proinflammatory mediators, including iNOS, COX-2, and microsomal PGE synthase-1. Therefore, targeting microglial activation, therefore, represents a promising strategy to enhance neuronal survival [46].

Treatment with TQ treatment (2.5, 5, and 10 mM) has been shown to suppress the NF-κB-dependent neuroinflammation in the BV2 microglial cells, which is done by reducing the protein expression of iNOS, as well as inhibiting phosphorylation of IκB, and preventing NF-κB from binding to DNA. However, TQ promoted the accumulation of Nrf2 and enhanced its binding to the ARE, which results in an increased ARE-driven transcriptional activity. These findings indicate that TQ exerts anti-inflammatory effects by the activation of the Nrf2/ARE pathway, which in turn inhibits the NF-κB-mediated neuroinflammation. Moreover, TQ reduced the LPS-induced neuroinflammatory responses by regulating the NF-κB signaling while simultaneously upregulate the activity of Nrf2 [37].

Additional studies have demonstrated that the administration of TQ (2.5, 5, and 10 mM) reduces the production of several inflammatory mediators, including NO, PGE₂, TNF-α, and IL-1β in BV2 microglial cells. Automatically, this anti-inflammatory action involves the inhibition of the PI3K/Akt/NF-κB signaling pathway in LPS-stimulated microglia, showing TQ as an important neuroprotective and anti-inflammatory agent in the context of AD [37].

TQ molecule exhibits a pro-apoptotic and cell cycle regulating effects that might have many implications in neurodegenerative conditions, including AD. Cancer preclinical research highlights the TQ’s ability to overcome chemotherapy resistance and enhance other standard therapies. This is done by the induction of cellular apoptosis, regulation of autophagy, endoplasmic reticulum (ER) stress modulation, unfolded protein response (UPR) modulation, and epigenetic regulation [47].

Primarily, TQ molecule suppresses cell proliferation through cell cycle arrest, microtubule organization disruption, and downregulation of pro-survival proteins [48]. The pro-apoptotic action involves mitochondrial dysfunction and activation of caspases, while regulating many pathways such as epithelial-mesenchymal transition (EMT) and oxidative stress, which may also play roles in neuronal protection and survival [49].

At the molecular level, TQ molecule induces cell cycle arrest by inhibiting the cyclin E and cyclin D activation while upregulating other cell cycle inhibitors such as p21 and p27, leading to G1-phase arrest. Notably, the concentration of TQ molecule determines the specific phase that is affected. The higher concentrations can induce G2-phase arrest, while lower doses may cause S-phase arrest in the proliferative cells [48]. Also, TQ upregulates the p53 protein in a time-dependent manner, since it can promote apoptosis via increased Bax expression, and downregulates the anti-apoptotic protein Bcl-2 [47].

These pathways suggest that TQ also may balance or neutralize the aberrant cell survival mechanisms, reduce pathological cellular stress, and promote programmed cell death of dysfunctional neurons, making it a promising molecule for neuroprotection in AD.