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| Lambertianic acid — a naturally occurring labdane-type diterpenoid carboxylic acid found in several conifer species, particularly Pinus koraiensis, Pinus lambertiana, and Platycladus orientalis. It is an experimental natural-product small molecule rather than an approved drug. The abbreviation LA is commonly used in the scientific literature, although the Nestronics product abbreviation is lamb. Lambertianic acid has reported anticancer, anti-inflammatory, anti-allergic, metabolic, and muscle-protective activities, but its therapeutic evidence remains predominantly cellular and preclinical. Its anticancer activity appears strongly context-dependent and involves coordinated effects on oxidative stress, AMPK signaling, cancer metabolism, STAT3/NF-κB survival signaling, androgen receptor signaling, and apoptosis. Primary mechanisms (ranked):
Bioavailability / PK relevance: Human pharmacokinetic parameters, oral bioavailability, plasma half-life, distribution, metabolism, and clinically achievable concentrations have not been adequately established. Lambertianic acid is a lipophilic diterpenoid and should therefore not be assumed to achieve the micromolar exposures used in cell-culture studies after ordinary dietary or oral exposure. No validated therapeutic dosing regimen exists. In-vitro vs systemic exposure relevance: Most anticancer experiments use approximately 10–200 µM lambertianic acid, depending on the model. Some signaling effects occur around 15–30 µM, whereas androgen-receptor prostate-cancer experiments used substantially higher concentrations, including approximately 100–200 µM. There is currently insufficient human PK evidence to demonstrate that these concentrations are systemically achievable. Normal-cell selectivity is also incompletely characterized; recent C2C12 studies found little cytotoxicity at 12.5–25 µM but measurable loss of viability at 50–100 µM. Clinical evidence status: Preclinical. Evidence consists primarily of cultured cancer cells with limited animal-supporting evidence from non-cancer metabolic studies. No established randomized clinical trial evidence, approved oncologic indication, validated human anticancer dose, or regulatory approval for lambertianic acid as a therapeutic agent was identified. Lambertianic Acid Mechanisms
P: 0–30 min R: 30 min–3 hr G: >3 hr |
| Source: TCGA |
| Type: Antiapoptotic |
| Nrf2 is responsible for regulating an extensive panel of antioxidant enzymes involved in the detoxification and elimination of oxidative stress. Thought of as "Master Regulator" of antioxidant response. -One way to estimate Nrf2 induction is through the expression of NQO1. NQO1, the most potent inducer: SFN 0.2 μM, quercetin (2.5 μM), curcumin (2.7 μM), Silymarin (3.6 μM), tamoxifen (5.9 μM), genistein (6.2 μM ), beta-carotene (7.2μM), lutein (17 μM), resveratrol (21 μM), indol-3-carbinol (50 μM), chlorophyll (250 μM), alpha-cryptoxanthin (1.8 mM), and zeaxanthin (2.2 mM) 1. Raising Nrf2 enhances the cell's antioxidant defenses and ↓ROS. This strategy is used to decrease chemo-radio side effects. 2. Downregulating Nrf2 lowers antioxidant defenses and ↑ROS. In cancer cells this leads to DNA damage, and cell death. 3. However there are some cases where increasing Nrf2 paradoxically causes an increase in ROS (cancer cells). Such as cases of Mitochondial overload, signal crosstalk, reductive stress -In some cases, Nrf2 is overexpressed in cancer cells, which can lead to the activation of genes involved in cell proliferation, angiogenesis, and metastasis. This can contribute to the development of resistance to chemotherapy and targeted therapies. -Increased Nrf2 expression: Lung, Breast, Colorectal, Prostrate. Decreased Nrf2 expression: Skine, Liver, Pancreatic. -Nrf2 is a cytoprotective transcription factor which demonstrated both a negative effect as well as a positive effect on cancer - "promotes Nrf2 translocation from the cytoplasm to the nucleus," means facilitates the movement of Nrf2 into the nucleus, thereby enhancing the cell's antioxidant and cytoprotective responses. -Major regulator of Nrf2 activity in cells is the cytosolic inhibitor Keap1. Nrf2 Inhibitors and Activators Nrf2 Inhibitors: Brusatol, Luteolin, Trigonelline, VitC, Retinoic acid, Chrysin Nrf2 Activators: SFN, OPZ EGCG, Resveratrol, DATS, CUR, CDDO, Api - potent Nrf2 inducers from plants include sulforaphane, curcumin, EGCG, resveratrol, caffeic acid phenethyl ester, wasabi, cafestol and kahweol (coffee), cinnamon, ginger, garlic, lycopene, rosemany Nrf2 plays dual roles in that it can protect normal tissues against oxidative damage and can act as an oncogenic protein in tumor tissue. – In healthy tissues, NRF2 activation helps protect cells from oxidative damage and maintains cellular homeostasis. – In many cancers, constitutive activation of NRF2 (often through mutations in NRF2 itself or loss-of-function mutations in KEAP1) leads to an enhanced antioxidant capacity. – This upregulation can promote tumor cell survival by enabling cancer cells to thrive under oxidative stress, resist chemotherapeutic agents, and sustain metabolic reprogramming. – Elevated NRF2 levels have been implicated in promoting tumor growth, metastasis, and resistance to therapy in various malignancies. – High or sustained NRF2 activity is frequently associated with aggressive tumor phenotypes, poorer prognosis, and decreased overall survival in several cancer types. – While its activation is essential for protecting normal cells from oxidative stress, aberrant or sustained NRF2 activation in tumor cells can lead to enhanced survival, therapeutic resistance, and tumor progression. NRF2 inhibitors: (to decrease antioxidant defenses and increase cell death from ROS). -Brusatol: most cited natural inhibitors of Nrf2. -Luteolin: luteolin can reduce Nrf2 activity in specific cancer models and may enhance cell sensitivity to chemotherapy. However, luteolin is also known as an antioxidant, and its influence on Nrf2 can sometimes be context dependent. -Apigenin: certain studies to down‑regulate Nrf2 in cancer cells: Dose and context dependent . -Oridonin: -Wogonin: although its effects might be cell‑ and dose‑specific. - Withaferin A |
| 8157- | lamb, | Pinus koraiensis leaf extract and lambertianic acid attenuate fatigue and improve endurance capacity via PI3K-mediated regulation of oxidative stress and mitochondrial biogenesis |
| - | in-vivo, | Nor, | 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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