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| Borneol is a bicyclic organic compound and a type of monoterpenoid that occurs naturally in various essential oils. -Recent studies have been exploring borneol’s ability to enhance drug delivery—especially across the blood-brain barrier. -Borneol is particularly known for its ability to act as a penetration enhancer. This quality can improve the absorption of various drugs, potentially increasing their efficacy when used in combination with other therapeutic agents. -Borneol is thought to temporarily open tight junctions between endothelial cells, enhancing drug penetration. It may also downregulate efflux transporters such as P-glycoprotein (P-gp), allowing higher intracellular concentrations of co-administered drugs. Sources: -Cinnamomum camphora (camphor tree), its essential oil contains borneol along with camphor. -Dryobalanops aromatica,Often referred to as the camphor tree in Southeast Asia, its oleoresin is a well-known source of natural borneol. -Blumea balsamifera -The introduction of borneol led to a significant reduction in the size of selenium nanoparticles (SeNPs), as documented in the study (Prabhakaret et al., 2013) -widely used as a messenger drug -Borneol is always used as an adjuvant in combination with other drugs to reduce the dosage of other drugs, increase their therapeutic effect, and decrease drug side effects Borneol — borneol is a bicyclic monoterpenoid alcohol present in several essential oils and also prepared synthetically; in biomedical use it functions less as a stand-alone anticancer drug than as a permeability enhancer, chemosensitizer, and CNS/brain-delivery adjuvant. It is best classified as a small-molecule natural product / terpene excipient-adjunct with pharmacologic activity. Standard abbreviations include BOR, BNL, and NB (natural borneol). Nestronics identifies the product as “born / borneol,” and the site notes its traditional sourcing from plants such as Cinnamomum camphora, Dryobalanops aromatica, and Blumea balsamifera. Across the current literature, borneol’s strongest translational niche is barrier modulation and drug co-delivery, especially toward the brain, while direct anticancer evidence remains preclinical. Primary mechanisms (ranked):
Bioavailability / PK relevance: Borneol is lipophilic, poorly water-soluble, and rapidly brain-penetrant, but oral administration showed the lowest absolute bioavailability among tested routes in mouse PK studies. Its main formulation value is therefore often as a permeation enhancer or co-formulation component rather than as a dependable high-exposure oral monotherapy. Intranasal, topical, trans-barrier, and carrier-based delivery have been investigated to exploit its barrier-opening properties.Nasal spray has been studied In-vitro vs systemic exposure relevance: Common in-vitro anticancer studies use roughly 10–80 μM borneol. Those concentrations are not obviously impossible relative to high-dose animal brain exposures, but they are often achieved in preclinical settings using aggressive dosing and do not establish practical or safe systemic anticancer exposure in humans. For borneol, the more reproducible translational effect is usually concentration-assisted delivery enhancement of a partner drug rather than robust single-agent cytotoxicity. . Clinical evidence status: Direct anticancer evidence is preclinical only. Human clinical evidence exists for non-cancer uses, including topical analgesia and borneol-containing cardiovascular/CNS formulations, but there is no established oncology approval or mature randomized cancer trial program supporting borneol as a stand-alone anticancer therapy. Mechanistic table
TSF legend P: 0–30 min R: 30 min–3 hr G: >3 hr |
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| Reactive oxygen species (ROS) are highly reactive molecules that contain oxygen and can lead to oxidative stress in cells. They play a dual role in cancer biology, acting as both promoters and suppressors of cancer. ROS can cause oxidative damage to DNA, leading to mutations that may contribute to cancer initiation and progression. So normally you want to inhibit ROS to prevent cell mutations. However excessive ROS can induce apoptosis (programmed cell death) in cancer cells, potentially limiting tumor growth. Chemotherapy typically raises ROS. -mitochondria is the main source of reactive oxygen species (ROS) (and the ETC is heavily related) "Reactive oxygen species (ROS) are two electron reduction products of oxygen, including superoxide anion, hydrogen peroxide, hydroxyl radical, lipid peroxides, protein peroxides and peroxides formed in nucleic acids 1. They are maintained in a dynamic balance by a series of reduction-oxidation (redox) reactions in biological systems and act as signaling molecules to drive cellular regulatory pathways." "During different stages of cancer formation, abnormal ROS levels play paradoxical roles in cell growth and death 8. A physiological concentration of ROS that maintained in equilibrium is necessary for normal cell survival. Ectopic ROS accumulation promotes cell proliferation and consequently induces malignant transformation of normal cells by initiating pathological conversion of physiological signaling networks. Excessive ROS levels lead to cell death by damaging cellular components, including proteins, lipid bilayers, and chromosomes. Therefore, both scavenging abnormally elevated ROS to prevent early neoplasia and facilitating ROS production to specifically kill cancer cells are promising anticancer therapeutic strategies, in spite of their contradictoriness and complexity." "ROS are the collection of derivatives of molecular oxygen that occur in biology, which can be categorized into two types, free radicals and non-radical species. The non-radical species are hydrogen peroxide (H 2O 2 ), organic hydroperoxides (ROOH), singlet molecular oxygen ( 1 O 2 ), electronically excited carbonyl, ozone (O3 ), hypochlorous acid (HOCl, and hypobromous acid HOBr). Free radical species are super-oxide anion radical (O 2•−), hydroxyl radical (•OH), peroxyl radical (ROO•) and alkoxyl radical (RO•) [130]. Any imbalance of ROS can lead to adverse effects. H2 O 2 and O 2 •− are the main redox signalling agents. The cellular concentration of H2 O 2 is about 10−8 M, which is almost a thousand times more than that of O2 •−". "Radicals are molecules with an odd number of electrons in the outer shell [393,394]. A pair of radicals can be formed by breaking a chemical bond or electron transfer between two molecules." Recent investigations have documented that polyphenols with good antioxidant activity may exhibit pro-oxidant activity in the presence of copper ions, which can induce apoptosis in various cancer cell lines but not in normal cells. "We have shown that such cell growth inhibition by polyphenols in cancer cells is reversed by copper-specific sequestering agent neocuproine to a significant extent whereas iron and zinc chelators are relatively ineffective, thus confirming the role of endogenous copper in the cytotoxic action of polyphenols against cancer cells. Therefore, this mechanism of mobilization of endogenous copper." > Ions could be one of the important mechanisms for the cytotoxic action of plant polyphenols against cancer cells and is possibly a common mechanism for all plant polyphenols. In fact, similar results obtained with four different polyphenolic compounds in this study, namely apigenin, luteolin, EGCG, and resveratrol, strengthen this idea. Interestingly, the normal breast epithelial MCF10A cells have earlier been shown to possess no detectable copper as opposed to breast cancer cells [24], which may explain their resistance to polyphenols apigenin- and luteolin-induced growth inhibition as observed here (Fig. 1). We have earlier proposed [25] that this preferential cytotoxicity of plant polyphenols toward cancer cells is explained by the observation made several years earlier, which showed that copper levels in cancer cells are significantly elevated in various malignancies. Thus, because of higher intracellular copper levels in cancer cells, it may be predicted that the cytotoxic concentrations of polyphenols required would be lower in these cells as compared to normal cells." Majority of ROS are produced as a by-product of oxidative phosphorylation, high levels of ROS are detected in almost all cancers. -It is well established that during ER stress, cytosolic calcium released from the ER is taken up by the mitochondrion to stimulate ROS overgeneration and the release of cytochrome c, both of which lead to apoptosis. Note: Products that may raise ROS can be found using this database, by: Filtering on the target of ROS, and selecting the Effect Direction of ↑ Targets to raise ROS (to kill cancer cells): • NADPH oxidases (NOX): NOX enzymes are involved in the production of ROS. -Targeting NOX enzymes can increase ROS levels and induce cancer cell death. -eNOX2 inhibition leads to a high NADH/NAD⁺ ratio which can lead to increased ROS • Mitochondrial complex I: Inhibiting can increase ROS production • P53: Activating p53 can increase ROS levels(by inducing the expression of pro-oxidant genes) • Nrf2 inhibition: regulates the expression of antioxidant genes. Inhibiting Nrf2 can increase ROS levels • Glutathione (GSH): an antioxidant. Depleting GSH can increase ROS levels • Catalase: Catalase converts H2O2 into H2O+O. Inhibiting catalase can increase ROS levels • SOD1: converts superoxide into hydrogen peroxide. Inhibiting SOD1 can increase ROS levels • PI3K/AKT pathway: regulates cell survival and metabolism. Inhibiting can increase ROS levels • HIF-1α inhibition: regulates genes involved in metabolism and angiogenesis. Inhibiting HIF-1α can increase ROS • Glycolysis: Inhibiting glycolysis can increase ROS levels • Fatty acid oxidation: Cancer cells often rely on fatty acid oxidation for energy production. -Inhibiting fatty acid oxidation can increase ROS levels • ER stress: Endoplasmic reticulum (ER) stress can increase ROS levels • Autophagy: process by which cells recycle damaged organelles and proteins. -Inhibiting autophagy can increase ROS levels and induce cancer cell death. • KEAP1/Nrf2 pathway: regulates the expression of antioxidant genes. -Inhibiting KEAP1 or activating Nrf2 can increase ROS levels and induce cancer cell death. • DJ-1: regulates the expression of antioxidant genes. Inhibiting DJ-1 can increase ROS levels • PARK2: regulates the expression of antioxidant genes. Inhibiting PARK2 can increase ROS levels • SIRT1 inhibition:regulates the expression of antioxidant genes. Inhibiting SIRT1 can increase ROS levels • AMPK activation: regulates energy metabolism and can increase ROS levels when activated. • mTOR inhibition: regulates cell growth and metabolism. Inhibiting mTOR can increase ROS levels • HSP90 inhibition: regulates protein folding and can increase ROS levels when inhibited. • Proteasome: degrades damaged proteins. Inhibiting the proteasome can increase ROS levels • Lipid peroxidation: a process by which lipids are oxidized, leading to the production of ROS. -Increasing lipid peroxidation can increase ROS levels • Ferroptosis: form of cell death that is regulated by iron and lipid peroxidation. -Increasing ferroptosis can increase ROS levels • Mitochondrial permeability transition pore (mPTP): regulates mitochondrial permeability. -Opening the mPTP can increase ROS levels • BCL-2 family proteins: regulate apoptosis and can increase ROS levels when inhibited. • Caspase-independent cell death: a form of cell death that is regulated by ROS. -Increasing caspase-independent cell death can increase ROS levels • DNA damage response: regulates the repair of DNA damage. Increasing DNA damage can increase ROS • Epigenetic regulation: process by which gene expression is regulated. -Increasing epigenetic regulation can increase ROS levels -PKM2, but not PKM1, can be inhibited by direct oxidation of cysteine 358 as an adaptive response to increased intracellular reactive oxygen species (ROS) ProOxidant Strategy:(inhibit the Mevalonate Pathway (likely will also inhibit GPx) -HydroxyCitrate (HCA) found as supplement online and typically used in a dose of about 1.5g/day or more -Atorvastatin typically 40-80mg/day, -Dipyridamole typically 200mg 2x/day Combined effect research -Lycopene typically 100mg/day range (note debatable as it mainly lowers NRF2) Dual Role of Reactive Oxygen Species and their Application in Cancer Therapy ROS-Inducing Interventions in Cancer — Canonical + Mechanistic Reference -generated from AI and Cancer database ROS rating: +++ strong | ++ moderate | + weak | ± mixed | 0 none NRF2: ↓ suppressed | ↑ activated | ± mixed | 0 none Conditions: [D] dose [Fe] metal [M] metabolic [O₂] oxygen [L] light [F] formulation [T] tumor-type [C] combination
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| 5660- | BNL, | Recent Progress on the Synergistic Antitumor Effect of a Borneol-Modified Nanocarrier Drug Delivery System |
| - | Review, | Var, | NA |
| 5671- | BNL, | (+)-Borneol inhibits the generation of reactive oxygen species and neutrophil extracellular traps induced by phorbol-12-myristate-13-acetate |
| - | in-vitro, | Nor, | NA |
| 5669- | BNL, | Comparison of pharmacological activity and safety of different stereochemical configurations of borneol: L-borneol, D-borneol, and synthetic borneol |
| - | Review, | Nor, | NA | - | Review, | AD, | NA | - | Review, | Stroke, | NA |
| 5668- | BNL, | Anticancer effect of borneol: Mechanistic insights through literature review and in silico studies |
| - | Review, | Var, | NA |
| - | vitro+vivo, | GBM, | U251 |
| 5653- | BNL, | Borneol hinders the proliferation and induces apoptosis through the suppression of reactive oxygen species-mediated JAK1 and STAT-3 signaling in human prostate cancer cells |
| - | in-vitro, | Pca, | PC3 |
| 5652- | BNL, | Borneol promotes apoptosis of Human Glioma Cells through regulating HIF-1a expression via mTORC1/eIF4E pathway |
| - | vitro+vivo, | GBM, | NA |
| 5651- | BNL, | Cisplatin, | Natural borneol sensitizes human glioma cells to cisplatin-induced apoptosis by triggering ROS-mediated oxidative damage and regulation of MAPKs and PI3K/AKT pathway |
| - | in-vitro, | GBM, | U251 | - | in-vitro, | GBM, | U87MG |
| 1948- | PL, | BNL, | Natural borneol serves as an adjuvant agent to promote the cellular uptake of piperlongumine for improving its antiglioma efficacy |
| - | in-vitro, | GBM, | NA |
Query results interpretion may depend on "conditions" listed in the research papers. Such Conditions may include : -low or high Dose -format for product, such as nano of lipid formations -different cell line effects -synergies with other products -if effect was for normal or cancerous cells
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