Description: <b>Andrographis</b> (typically referring to Andrographis paniculata).<br>
Bitter tasting annual plant prevalent in much of Asia.<br>
Andrographis paniculata is a medicinal plant whose principal bioactive diterpenoid lactone is andrographolide. It is widely studied for anti-inflammatory and immunomodulatory effects, and in preclinical oncology models is reported to modulate NF-κB, JAK/STAT3, PI3K/AKT, MAPK, and cell-cycle pathways, with downstream effects on apoptosis, invasion, and angiogenesis.<br
Oral bioavailability of andrographolide is limited, and many in-vitro anticancer concentrations exceed typical plasma levels achieved with standard supplementation.<br
<br
<a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC4032030/">"used traditionally for the treatment of array of diseases such as cancer, diabetes, high blood pressure, ulcer, leprosy, bronchitis, skin diseases, flatulence, colic, influenza, dysentery, dyspepsia and malaria for centuries in Asia, America and Africa continents."</a><br>
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Andrographolide:<br>
– Is a specific diterpenoid lactone and the major active constituent extracted from Andrographis paniculata.<br>
– It is responsible for many of the therapeutic effects attributed to the plant, including anti-inflammatory and antioxidant properties.<br>
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A. Anti-Inflammatory Effects.<br>
• Andrographolide has been shown to inhibit the NF-κB pathway, leading to a reduction in the transcription of inflammatory cytokines (e.g., TNF-α, IL-6).<br>
• Andrographolide has been reported to cause cell cycle arrest at critical checkpoints (such as G0/G1 or G2/M phase) in some cancer cell models.<br>
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Andrographis, primarily through its active constituent andrographolide, offers compelling anti-inflammatory, immunomodulatory, pro-apoptotic, and antiproliferative properties. While not a standard anticancer agent, its capacity to modulate key pathways in cellular stress response and inflammation makes it an attractive candidate for complementary research in oncology.<br>
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Andrographis paniculata, also known as the "King of Bitters," is a plant native to India and Southeast Asia. Its aqueous extract, Andrographis paniculata aqueous extract (APAE), has been studied for its potential anti-cancer properties.<br>
• Inhibition of cancer cell growth: APAE has been shown to inhibit the growth of various cancer cell lines, including breast, lung, colon, and prostate cancer cells.<br>
• Induction of apoptosis: APAE has been found to induce apoptosis (programmed cell death) in cancer cells, which may help to prevent tumor growth and progression.<br>
• Anti-inflammatory effects: APAE has anti-inflammatory properties, which may help to reduce the risk of cancer development and progression.<br>
• Antioxidant activity: APAE has antioxidant activity, which may help to protect against oxidative stress and DNA damage.<br>
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Key compounds:Andrographolide, Neoandrographolide<br>
APAE may interact with certain medications, including blood thinners and diabetes medications, and may not be suitable for individuals with certain medical conditions, such as autoimmune disorders.<br>
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<!-- Andrographis (Andrographolide) — Time-Scale Flagged Pathway Table -->
<table border="1" cellpadding="4" cellspacing="0">
<tr>
<th>Rank</th>
<th>Pathway / Axis</th>
<th>Cancer / Tumor Context</th>
<th>Normal Tissue Context</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, cytokines, Bcl-2 family ↓ (reported)</td>
<td>Inflammation tone ↓</td>
<td>R, G</td>
<td>Anti-inflammatory + anti-survival transcription</td>
<td>One of the most consistently reported mechanisms; contributes to reduced tumor-promoting inflammation.</td>
</tr>
<tr>
<td>2</td>
<td>JAK/STAT3 signaling</td>
<td>STAT3 activation ↓ (reported)</td>
<td>↔</td>
<td>R, G</td>
<td>Oncogenic transcription suppression</td>
<td>STAT3 inhibition is frequently reported in tumor models and linked to reduced proliferation and survival.</td>
</tr>
<tr>
<td>3</td>
<td>PI3K → AKT (± mTOR)</td>
<td>PI3K/AKT signaling ↓ (model-dependent)</td>
<td>↔</td>
<td>R, G</td>
<td>Growth/survival modulation</td>
<td>Often described as downstream of inflammatory signaling suppression.</td>
</tr>
<tr>
<td>4</td>
<td>MAPK pathways (ERK / JNK / p38)</td>
<td>MAPK modulation (context-dependent)</td>
<td>↔</td>
<td>P, R, G</td>
<td>Signal reprogramming</td>
<td>Stress MAPKs (JNK/p38) frequently activated; ERK modulation varies by cell type and dose.</td>
</tr>
<tr>
<td>5</td>
<td>Cell-cycle arrest (G0/G1 or G2/M)</td>
<td>Cell-cycle arrest ↑ (reported)</td>
<td>↔</td>
<td>G</td>
<td>Cytostasis</td>
<td>Often associated with Cyclin D1/CDK downregulation and checkpoint protein modulation.</td>
</tr>
<tr>
<td>6</td>
<td>Intrinsic apoptosis (mitochondrial pathway)</td>
<td>Apoptosis ↑; Bax ↑; caspases ↑ (reported)</td>
<td>↔ (generally less activation)</td>
<td>G</td>
<td>Cell death execution</td>
<td>Frequently observed downstream of survival pathway inhibition and stress signaling.</td>
</tr>
<tr>
<td>7</td>
<td>ROS modulation</td>
<td>ROS ↑ or ↓ depending on context</td>
<td>Antioxidant support in inflammatory models</td>
<td>P, R, G</td>
<td>Redox modulation</td>
<td>Andrographolide may induce ROS in some tumor cells but act antioxidant in inflammatory settings; context-dependent.</td>
</tr>
<tr>
<td>8</td>
<td>Invasion / metastasis (MMPs / EMT)</td>
<td>MMP2/MMP9 ↓; migration/invasion ↓ (reported)</td>
<td>↔</td>
<td>G</td>
<td>Anti-invasive phenotype</td>
<td>Often linked to NF-κB and STAT3 pathway suppression.</td>
</tr>
<tr>
<td>9</td>
<td>Angiogenesis signaling (VEGF)</td>
<td>VEGF ↓ (reported)</td>
<td>↔</td>
<td>G</td>
<td>Anti-angiogenic support</td>
<td>Generally secondary to inflammatory and survival pathway changes.</td>
</tr>
<tr>
<td>10</td>
<td>Bioavailability constraint</td>
<td>Low oral bioavailability; rapid metabolism</td>
<td>—</td>
<td>—</td>
<td>Translation constraint</td>
<td>Plasma levels after oral dosing are typically lower than many in-vitro cytotoxic concentrations.</td>
</tr>
</table>
<p><b>Time-Scale Flag (TSF):</b> P / R / G</p>
<ul>
<li><b>P</b>: 0–30 min (rapid signaling interactions)</li>
<li><b>R</b>: 30 min–3 hr (acute transcription and stress-response shifts)</li>
<li><b>G</b>: >3 hr (gene-regulatory adaptation and phenotype-level outcomes)</li>
</ul>