Description: <b>Baicalin</b> is a flavone glycoside, it is a flavonoid. It is the glucuronide of baicalein.
Baicalin is a flavonoid glycoside derived from plants in the genus Scutellaria. It has anxiolytic, anti-cancer and anti-viral properties, and is used in traditional Chinese medicine.<br>
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Baicalein and baicalin are chemically related, with baicalin being essentially a conjugated (sugar-attached) form of baicalein. This conjugation can modify their biological functions and impacts, making them distinct in certain aspects even though they share several pharmacological properties.<br>
baicalin is often hydrolyzed by gut β-glucuronidase to baicalein (aglycone) and then extensively converted to phase-II conjugates (glucuronides/sulfates), which constrains systemic “free” levels after oral dosing.
In cancer models, baicalin/baicalein are reported to modulate NF-κB, PI3K/AKT/mTOR, MAPK, and related programs, with downstream effects on cell-cycle arrest, apoptosis, invasion/EMT, and angiogenesis (model-dependent).<br>
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Baicalein appears to be antioxidant in normal cells (low Cu). In vitro, baicalein can participate in copper-dependent redox cycling under high Cu conditions, leading to ROS generation. Whether this mechanism contributes meaningfully in vivo remains model-dependent. (higher Cu levels) (May applies to other plant polyphenols as well: Ex apigenin, luteolin, EGCG, and resveratrol).<br>
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Pathways:<br>
Apoptosis Pathways (Intrinsic/Mitochondrial):<br>
NF-κB Inhibition :<br>
PI3K/Akt/mTOR Signaling Pathway downregulate :<br>
MAPK/ERK and JNK Signaling Pathways:<br>
STAT3 Signaling: (inhibit)<br>
Wnt/β-Catenin Signaling Pathway: (suppress)<br>
Other Pathways and Effects:<br>
• Cell Cycle Arrests (commonly G0/G1 or G2/M)<br>
• Anti-angiogenic Effects: By inhibiting VEGF<br>
• Modulation of Oxidative Stress: Balancing reactive oxygen species (ROS) levels in cancer cells can also contribute to its antitumor effects.<br>
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• In normal cells or under conditions of oxidative stress, baicalin has been shown to act as an antioxidant.<br>
• In cancer cells, baicalin may increase ROS levels, triggering apoptosis.
Lower doses of baicalin might favor antioxidant responses, whereas higher concentrations could lead to ROS accumulation in cancer cells.
Redox effects are concentration- and context-dependent; antioxidant behavior predominates in non-tumor oxidative stress models, whereas ROS increases have been reported in some tumor systems at higher concentrations.<br>
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• If copper levels are elevated in a cancer cell, the additional ROS generated via copper-mediated reactions may synergize with baicalin’s pro-oxidant effects (if observed at higher doses) to exceed the threshold for cancer cell survival.<br>
• Conversely, in normal cells with tightly regulated copper levels, baicalin’s antioxidant properties may help in quenching excess ROS or maintaining redox balance.<br>
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-IC50 in cancer cell lines: Approximately 50–200 µM (with some variability depending on the cell type).<br>
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• IC50 in normal cell lines: Generally higher, often exceeding 200 µM, though values will vary with experimental conditions.
Many in-vitro IC50 values exceed achievable systemic concentrations after oral dosing without advanced formulation.<br>
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Low oral bioavailability: classic rat PK reports very low absolute BA bioavailability and evidence of enterohepatic cycling<br>
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<!-- Baicalin (BAI) — Time-Scale Flagged Pathway Table (web-page ready) -->
<table border="1" cellpadding="4" cellspacing="0">
<tr>
<th>Rank</th>
<th>Pathway / Axis</th>
<th>Cancer Cells</th>
<th>Normal Cells</th>
<th>TSF</th>
<th>Primary Effect</th>
<th>Notes / Interpretation</th>
</tr>
<tr>
<td>1</td>
<td>NF-κB inflammatory / survival transcription</td>
<td>NF-κB ↓; COX-2/iNOS/cytokine programs ↓ (reported)</td>
<td>Inflammation tone ↓ (common in injury models)</td>
<td>R, G</td>
<td>Anti-inflammatory + anti-survival transcription</td>
<td>Frequently reported across inflammation and tumor models; strength depends on model/exposure and whether effects are driven by baicalein metabolites.</td>
</tr>
<tr>
<td>2</td>
<td>PI3K → AKT → mTOR survival axis</td>
<td>PI3K/AKT/mTOR tone ↓ (reported; model-dependent)</td>
<td>↔</td>
<td>R, G</td>
<td>Growth/survival modulation</td>
<td>Often presented as a key “oncogenic survival” axis modulated by baicalin/baicalein; keep “reported/model-dependent.”</td>
</tr>
<tr>
<td>3</td>
<td>MAPK re-wiring (ERK / JNK / p38)</td>
<td>MAPK modulation (context-dependent)</td>
<td>↔</td>
<td>P, R, G</td>
<td>Signal reprogramming</td>
<td>Directions vary across cell type, dose, and stress context; avoid fixed arrows without model-specific citations.</td>
</tr>
<tr>
<td>4</td>
<td>Nrf2/ARE antioxidant response (HO-1, GSH systems)</td>
<td>Stress adaptation modulation (context-dependent)</td>
<td>Nrf2 ↑; antioxidant defenses ↑</td>
<td>R, G</td>
<td>Redox buffering</td>
<td>Often described as antioxidant/anti-inflammatory; in tumors, Nrf2 direction/benefit is context-dependent.</td>
</tr>
<tr>
<td>5</td>
<td>Cell-cycle checkpoints (Cyclins/CDKs; S or G1/G2 arrest)</td>
<td>Cell-cycle arrest ↑ (reported; phase varies)</td>
<td>↔</td>
<td>G</td>
<td>Cytostasis</td>
<td>Common phenotype-level endpoint; typically downstream of survival signaling changes.</td>
</tr>
<tr>
<td>6</td>
<td>Intrinsic apoptosis (mitochondrial/caspase linked)</td>
<td>Apoptosis ↑; caspases ↑ (reported)</td>
<td>↔ (generally less activation)</td>
<td>G</td>
<td>Cell death execution</td>
<td>Frequently reported in vitro; magnitude depends strongly on achievable intracellular exposure.</td>
</tr>
<tr>
<td>7</td>
<td>Invasion / metastasis programs (MMPs / EMT; Wnt/β-catenin reported)</td>
<td>MMPs ↓; EMT/migration/invasion ↓ (reported)</td>
<td>↔</td>
<td>G</td>
<td>Anti-invasive phenotype</td>
<td>Often linked to NF-κB/PI3K/MAPK changes; Wnt/β-catenin modulation is reported in some systems.</td>
</tr>
<tr>
<td>8</td>
<td>Angiogenesis signaling (VEGF & related outputs)</td>
<td>VEGF / angiogenic outputs ↓ (reported)</td>
<td>↔</td>
<td>G</td>
<td>Anti-angiogenic support</td>
<td>Usually a later phenotype-level effect tied to inflammatory/survival signaling modulation.</td>
</tr>
<tr>
<td>9</td>
<td>Autophagy modulation (stress adaptation)</td>
<td>Autophagy ↑ or ↓ depending on model; can affect sensitivity to therapy</td>
<td>↔</td>
<td>G</td>
<td>Adaptive stress response</td>
<td>Reported in multiple cancer systems but direction is heterogeneous; keep model-qualified.</td>
</tr>
<tr>
<td>10</td>
<td>Bioavailability / metabolism constraint (baicalin ↔ baicalein; conjugates; enterohepatic cycling)</td>
<td>Systemic “free” levels often low; extensive glucuronidation/sulfation</td>
<td>—</td>
<td>—</td>
<td>Translation constraint</td>
<td>Oral baicalin shows low absolute bioavailability in animal PK; gut microbiota hydrolysis to baicalein and extensive phase-II metabolism dominate exposure, with enterohepatic cycling reported.</td>
</tr>
</table>
<p><b>Time-Scale Flag (TSF):</b> P / R / G</p>
<ul>
<li><b>P</b>: 0–30 min (rapid signaling/redox interactions)</li>
<li><b>R</b>: 30 min–3 hr (acute transcription + stress-response signaling shifts)</li>
<li><b>G</b>: >3 hr (gene-regulatory adaptation and phenotype outcomes)</li>
</ul>