| Features: |
| The (R)-enantiomer of alkannin is known as shikonin, and the racemic mixture of the two is known as shikalkin. Shikonin is a naphthoquinone derivative primarily isolated from the roots of plants in the Boraginaceae family (e.g., Lithospermum erythrorhizon). Shikonin is the main active component of a Chinese medicinal plant 'Zi Cao' -Shikonin is a major component of zicao (purple gromwell, the dried root of Lithospermum erythrorhizon), a Chinese herbal medicine with anti-inflammatory properties -Quinone methides (QMs) are highly reactive intermediates formed from natural compounds like shikonin -ic50 cancer cells 1-10uM, normal cells >10uM -known as Glycolysis inhibitor: ( inhibit pyruvate kinase M2 (PKM2*******), a key enzyme in the glycolytic pathway) Available from mcsformulas.com Shikonin Pro Liposomal, 30 mg Also In Glycolysis Inhibithree(100 mg PHLORIZIN,10 mg TANSHINONE IIA, 8 mg Shikonin) -Note half-life15-30mins or 8hr?. BioAv low, poor water solubility Pathways: - usually induce ROS production in cancer cells, and reduce ROS in normal cells. - ROS↑ related: MMP↓(ΔΨm), ER Stress↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓, - Lowers AntiOxidant defense in Cancer Cells: NRF2↓, TrxR↓**, SOD↓, GSH↓ Catalase↓ GPx4↓ - Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑, - lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : NLRP3↓, IL-1β↓, TNF-α↓, IL-6↓, IL-8↓ - inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, IGF-1↓, uPA↓, VEGF↓, FAK↓, NF-κB↓, TGF-β↓, ERK↓ - cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, - inhibits Migration/Invasion : TumCMig↓, TumCI↓, FAK↓, ERK↓, EMT↓, - inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDH">LDHA↓, HK2↓, PFKs↓, PDKs↓, ECAR↓, OXPHOS↓, GRP78↑, GlucoseCon↓ - inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, EGFR↓, Integrins↓, - Others: PI3K↓, AKT↓, JAK↓, STAT↓, β-catenin↓, AMPK, ERK↓, JNK, P53↑, - Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective, - Selectivity: Cancer Cells vs Normal Cells |
| Source: |
| Type: |
| LDH is a general term that refers to the enzyme that catalyzes the interconversion of lactate and pyruvate. LDH is a tetrameric enzyme, meaning it is composed of four subunits. LDH refers to the enzyme as a whole, while LDHA specifically refers to the M subunit. Elevated LDHA levels are often associated with poor prognosis and aggressive tumor behavior, similar to elevated LDH levels. However, it's worth noting that some studies have shown that LDHA is a more specific and sensitive biomarker for cancer than total LDH, as it is more closely associated with the Warburg effect and cancer metabolism. Dysregulated LDH activity contributes significantly to cancer development, promoting the Warburg effect (Chen et al., 2007), which involves increased glucose uptake and lactate production, even in the presence of oxygen, to meet the energy demands of rapidly proliferating cancer cells (Warburg and Minami, 1923; Dai et al., 2016b). LDHA overexpression favors pyruvate to lactate conversion, leading to tumor microenvironment acidification and aiding cancer progression and metastasis. Inhibitors: Flavonoids, a group of polyphenols abundant in fruit, vegetables, and medicinal plants, function as LDH inhibitors. • Galloflavin: A flavonoid compound found in the plant Galphimia gracilis, which has been shown to inhibit LDH and have anti-cancer activity. • Fisetin: A flavonoid compound found in various fruits and vegetables, which has been shown to inhibit LDH and have anti-cancer activity. • Quercetin: A flavonoid compound found in various fruits and vegetables, which has been shown to inhibit LDH and have anti-cancer activity. • Kaempferol: A flavonoid compound found in various fruits and vegetables, which has been shown to inhibit LDH and have anti-cancer activity. • Resveratrol: A polyphenol compound found in grapes and other plants, which has been shown to inhibit LDH and have anti-cancer activity. • Curcumin: A polyphenol compound found in turmeric, which has been shown to inhibit LDH and have anti-cancer activity. • Berberine: A compound found in the plant Berberis, which has been shown to inhibit LDH and have anti-cancer activity. • Honokiol: A lignan compound found in the plant Magnolia, which has been shown to inhibit LDH and have anti-cancer activity. • Silibinin: A flavonoid compound found in milk thistle, which has been shown to inhibit LDH and have anti-cancer activity. Others:Ursolic acid, Oleanolic acid, Limonin, Allicin (garlic), Taurine |
| 3040- | SK, | Pharmacological Properties of Shikonin – A Review of Literature since 2002 |
| - | Review, | Var, | NA | - | Review, | IBD, | NA | - | Review, | Stroke, | NA |
| 2181- | SK, | Shikonin and its analogs inhibit cancer cell glycolysis by targeting tumor pyruvate kinase-M2 |
| - | in-vitro, | BC, | MCF-7 | - | in-vitro, | Lung, | A549 | - | in-vitro, | Cerv, | HeLa |
| 1284- | SK, | Shikonin induces ferroptosis in multiple myeloma via GOT1-mediated ferritinophagy |
| - | in-vitro, | Melanoma, | RPMI-8226 | - | in-vitro, | Melanoma, | U266 |
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