# Andrographolide (from Andrographis paniculata)

**Canonical URL:** https://ingredients.hermeticasuperfoods.com/ingredients/andrographolide-from-andrographis-paniculata
**Data Source:** Hermetica Superfoods Ingredient Encyclopedia
**Updated:** 2026-04-02
**Evidence Score:** 1 / 10
**Category:** Compound
**Also Known As:** Andrographis paniculata diterpenoid, C₂₀H₃₀O₅, Andrographolide lactone, AP bioactive compound, Kalmegh active constituent, Chuanxinlian diterpenoid

## Overview

Andrographolide (C₂₀H₃₀O₅) is a bicyclic diterpenoid lactone that exerts [anti-inflammatory](/ingredients/condition/inflammation) and [immunomodulatory](/ingredients/condition/immune-support) effects primarily through inhibition of NF-κB signaling, suppression of TNF-α and IL-12 production, and blockade of ERK1/2 and PI3K/Akt pathways. In a Phase I dose-escalating clinical trial in HIV-positive patients, andrographolide supplementation produced a statistically significant rise in mean CD4⁺ lymphocyte counts, and in vitro exposure at 1 µM increased human peripheral blood lymphocyte proliferation by 14% via IL-2 induction.

## Health Benefits

- **Anti-Inflammatory Activity**: Andrographolide inhibits NF-κB nuclear translocation and suppresses downstream [pro-inflammatory cytokine](/ingredients/condition/inflammation)s TNF-α and IL-12, reducing neutrophil oxygen radical production and macrophage migration in preclinical models.
- **[Immunomodulat](/ingredients/condition/immune-support)ion**: At 1 µM, andrographolide induces IL-2 secretion in human peripheral blood lymphocytes, increasing cell proliferation by 14%, with potential applications in immune-compromised conditions including HIV infection.
- **[Hepatoprotect](/ingredients/condition/detox)ion**: Preclinical studies consistently demonstrate andrographolide's ability to protect hepatocytes against chemical-induced injury through antioxidant mechanisms and suppression of inflammatory signaling, supporting its long-standing traditional use in liver disorders.
- **Antioxidant Effects**: Purified andrographolide demonstrates an IC₅₀ of 3.2 mg/mL for DPPH [free radical scaveng](/ingredients/condition/antioxidant)ing, substantially outperforming crude plant extracts (IC₅₀ ~220.5 mg/mL), with total free radical scavenging in standardized extracts ranging from 77.66–89.28%.
- **Anticancer Potential (Preclinical)**: Andrographolide exhibits cytotoxic activity against colorectal cancer cells (CACO-2) with an IC₅₀ of 32.46 µg/mL in vitro, likely mediated through NF-κB inhibition and disruption of cell cycle progression.
- **Antihypertensive Effects**: In vitro studies report up to 94% inhibition of angiotensin-converting enzyme (ACE) activity by andrographolide-rich fractions, suggesting a mechanism relevant to [blood pressure regulation](/ingredients/condition/heart-health) that warrants clinical investigation.
- **Anti-HIV Activity**: Andrographolide demonstrated an EC₅₀ of 49 µg/mL against HIV replication in vitro, and a Phase I trial reported significant CD4⁺ lymphocyte elevation attributed to inhibition of HIV-induced cell cycle dysregulation.

## Mechanism of Action

Andrographolide's primary [anti-inflammatory](/ingredients/condition/inflammation) mechanism involves covalent interaction with cysteine residues on IκB kinase β (IKKβ), preventing phosphorylation and degradation of IκBα and thereby blocking NF-κB nuclear translocation and transcription of pro-inflammatory genes including TNF-α, IL-1β, and IL-12. It concurrently inhibits protein kinase C, ERK1/2 MAPK, and PI3K/Akt signaling cascades, collectively attenuating oxidative burst in neutrophils and chemotactic migration of macrophages. At low concentrations (1 µM), andrographolide upregulates IL-2 gene expression in T-lymphocytes, promoting lymphocyte proliferation and adaptive immune responses, while at higher concentrations cytotoxic effects predominate, suggesting a biphasic [immunomodulatory](/ingredients/condition/immune-support) profile. The compound's lactone moiety is essential for its bioactivity, forming Michael adducts with thiol groups on target proteins, and semi-synthetic analogues such as 14-deoxy-11,12-didehydroandrographolide exhibit enhanced immunostimulatory and anti-infective activities relative to the parent molecule.

## Clinical Summary

The most clinically informative human data for andrographolide comes from a Phase I dose-escalating trial in HIV-positive patients, where the compound produced a statistically significant rise in CD4⁺ lymphocyte levels, suggesting biological activity at doses tolerated in humans. Human pharmacokinetic data from a 200 mg oral dose study established a C_max of 58.62 ng/mL at Tmax 1.6 hours and a terminal half-life of 10.50 hours, supporting twice-daily dosing intervals. In vitro human lymphocyte studies found that 1 µM andrographolide increased HPBL proliferation by 14% and induced IL-2, providing mechanistic corroboration of the immune-enhancing signal seen clinically. Overall, clinical evidence remains limited to early-phase trials and cell-based human studies; well-powered Phase II/III randomized controlled trials are needed before efficacy claims can be made with high confidence for any indication.

## Nutritional Profile

Andrographolide itself is a pure diterpenoid lactone compound (C₂₀H₃₀O₅, MW 350.45 g/mol) with no direct macronutrient contribution; in the context of whole Andrographis paniculata plant material, the nutritional profile includes the following bioactive constituents: andrographolide at 0.5–6% in dried leaves and up to 14.47% in optimized aerial part extracts; neoandrographolide at up to 110.77 mg/g in optimized methanolic fractions; 14-deoxy-11,12-didehydroandrographolide at up to 49.19 mg/g; andrograpanin at up to 17.39 mg/g; and flavonoids including myricetin at approximately 0.3190% in stem extracts. Over 20 distinct diterpenoids and flavonoids have been identified across plant parts. Bioavailability of andrographolide is critically limited by its lipophilicity and first-pass hepatic [metabolism](/ingredients/condition/weight-management), with absolute oral bioavailability of approximately 1.19% in rodent models, though enhanced formulations can dramatically improve dissolution and presumptive absorption.

## Dosage & Preparation

- **Standardized Extract (oral capsule/tablet)**: Most commercial products are standardized to 10–30% andrographolide content; typical doses used in preclinical efficacy studies translate to ~100–400 mg extract daily in adults, though no universally accepted human therapeutic dose has been established.
- **Purified Andrographolide (research/Phase I)**: Oral doses studied in humans include 200 mg as a single dose for pharmacokinetic profiling; escalating doses were used in the HIV Phase I trial without specified upper limits in available reports.
- **Animal Study Reference Doses**: 50–100 mg/kg body weight in rats achieved plasma C_max of ~1 µM at 30 minutes, with absolute oral bioavailability of only 1.19%, underscoring that human-equivalent doses require bioavailability-enhanced formulations.
- **Optimized Liquid/Pellet Formulations**: Proprietary formulations with absorption enhancers achieved 97.64–97.74% dissolution within 15 minutes versus 10% for crude extract in 2 hours; these are preferable for maximum systemic exposure.
- **Traditional Decoction (Ayurveda/TCM)**: Dried aerial parts of Andrographis paniculata are decocted in water (3–9 g dried herb per day in TCM; kalamegh churna 1–3 g twice daily in Ayurveda), delivering andrographolide alongside neoandrographolide and other diterpenoids.
- **Bioavailability Note**: Natural oral bioavailability is poor (~1.19% in rats) due to high lipophilicity and extensive first-pass [metabolism](/ingredients/condition/weight-management); co-administration with lipid-based carriers or piperine may improve absorption.
- **Timing**: Based on Tmax of 1.6 hours in humans, administration with meals may modulate absorption; twice-daily dosing aligns with the 10.5-hour half-life observed in human pharmacokinetic studies.

## Safety & Drug Interactions

At doses used in the Phase I HIV trial, andrographolide appeared generally well-tolerated with an acceptable safety profile; however, cytotoxicity has been documented in human peripheral blood lymphocytes at concentrations above the immunostimulatory range of 1 µM, indicating a narrow therapeutic window that requires careful dosing. Known potential drug interactions include additive hypotensive effects with antihypertensive agents (given andrographolide's 94% ACE inhibition in vitro) and theoretical potentiation of anticoagulant or antiplatelet drugs through platelet aggregation inhibition pathways reported in preclinical data. Andrographolide is contraindicated in pregnancy due to preclinical evidence of uterine contractile activity and potential abortifacient effects; lactating women should also avoid supplementation pending adequate safety data. Hepatotoxic effects have not been reported at conventional doses, and the compound is traditionally regarded as [hepatoprotective](/ingredients/condition/detox), but chronic high-dose exposure in rats resulted in rapid tissue accumulation particularly in the kidney (C_max 115.81 ng/mL), and the long-term safety implications of such tissue accumulation in humans have not been systematically studied.

## Scientific Research

The evidentiary base for andrographolide consists predominantly of in vitro cell culture studies and animal pharmacology experiments, with only limited human clinical data available; this places overall evidence strength in the preliminary-to-moderate range. A Phase I dose-escalating trial in HIV-positive individuals reported significant increases in mean CD4⁺ lymphocyte counts following andrographolide administration, providing the most direct human efficacy signal, though sample sizes and precise effect magnitudes were not fully detailed in available reports. Pharmacokinetic studies in humans have characterized oral bioavailability following a 200 mg dose, yielding a C_max of 58.62 ng/mL at 1.6 hours and a half-life of 10.50 hours, which provides a rational basis for dosing interval selection. Optimized formulations (liquid-filled and pellet-based) have demonstrated dramatically improved in vitro dissolution (97.64–97.74% within 15 minutes versus 10% over 2 hours for crude extract), though whether this translates to proportional clinical benefit in controlled trials has not yet been established.

## Historical & Cultural Context

Andrographis paniculata, the source plant of andrographolide, has been used for over two millennia in Ayurvedic medicine under the name 'kalmegh' (meaning 'king of bitters') and in Siddha medicine, where it was prescribed as a bitter tonic, antipyretic, and liver-protective agent for fevers, jaundice, dysentery, and respiratory infections. In Traditional Chinese Medicine it is known as 'Chuanxinlian' and has been listed in the Chinese Pharmacopoeia, prescribed as a heat-clearing and detoxifying herb for infections, sore throat, and diarrhea, with significant use during the 1970s Chinese campaigns against influenza and bacterial dysentery. The isolated compound andrographolide was first characterized chemically in the mid-20th century, with its diterpenoid lactone structure elucidated through X-ray crystallography, enabling targeted pharmacological investigation separate from the whole-plant preparations used traditionally. The plant's extreme bitterness — attributed largely to andrographolide and its analogues — led to its Sanskrit epithet 'Maha-tikta' (the great bitter), and traditional preparations included fresh juice, powders, and decoctions prepared from aerial parts harvested before flowering to maximize diterpenoid content.

## Synergistic Combinations

Andrographolide combined with piperine (from black pepper) may enhance oral bioavailability by inhibiting P-glycoprotein-mediated efflux and CYP3A4-mediated first-pass [metabolism](/ingredients/condition/weight-management), a strategy documented for other poorly bioavailable phytochemicals and theoretically applicable given andrographolide's similarly low natural bioavailability of ~1.19%. In traditional Ayurvedic formulations, Andrographis paniculata is frequently co-administered with Tinospora cordifolia (guduchi) and Phyllanthus niruri, with the combination hypothesized to provide additive [hepatoprotective](/ingredients/condition/detox) and [immunomodulatory](/ingredients/condition/immune-support) effects through complementary NF-κB and [oxidative stress](/ingredients/condition/antioxidant) pathway inhibition. Andrographolide's NF-κB inhibitory activity may synergize with omega-3 fatty acids (EPA/DHA), which suppress NF-κB through independent lipid mediator pathways (resolvins, protectins), representing a mechanistically rational [anti-inflammatory](/ingredients/condition/inflammation) stack.

## Frequently Asked Questions

### What does andrographolide do in the body?

Andrographolide inhibits the NF-κB transcription factor by blocking IκB kinase β (IKKβ), which prevents the expression of pro-inflammatory cytokines including TNF-α, IL-1β, and IL-12. It also suppresses ERK1/2 MAPK and PI3K/Akt signaling, reducing oxidative burst in neutrophils and macrophage migration. At low concentrations (1 µM), it additionally induces IL-2 in T-lymphocytes, boosting adaptive immune cell proliferation by approximately 14%.

### What is the recommended dosage of andrographolide?

No universally established therapeutic dose exists for andrographolide as an isolated compound in humans. A 200 mg oral single dose has been studied pharmacokinetically, yielding a peak plasma concentration of 58.62 ng/mL at 1.6 hours with a half-life of 10.50 hours. For standardized Andrographis paniculata extracts, commercial products typically deliver 10–30% andrographolide content, with total extract doses ranging from 100–400 mg per day in clinical practice, though dosing should be guided by a qualified healthcare provider.

### Is andrographolide safe to take, and are there side effects?

Andrographolide appeared generally safe in a Phase I dose-escalating trial in HIV-positive patients. However, high concentrations are cytotoxic to human lymphocytes in vitro, suggesting a concentration-dependent safety threshold. It should not be used during pregnancy due to preclinical evidence of uterine contractile activity, and caution is warranted when combining it with antihypertensive drugs or anticoagulants due to potential additive effects.

### Why is andrographolide poorly absorbed, and how can absorption be improved?

Andrographolide has very low oral bioavailability — approximately 1.19% in rodent models — due to its high lipophilicity and extensive first-pass hepatic metabolism. Crude extracts show only ~10% dissolution after 2 hours in standard testing. Optimized liquid-filled capsule or pellet formulations with absorption enhancers achieve 97.64–97.74% dissolution within 15 minutes; co-administration with piperine may further inhibit P-glycoprotein efflux and CYP3A4 metabolism to improve systemic exposure.

### What is the difference between andrographolide and Andrographis paniculata extract?

Andrographis paniculata extract is a complex mixture containing over 20 diterpenoids and flavonoids, including andrographolide (0.5–6% in leaves), neoandrographolide (up to 110.77 mg/g in optimized fractions), 14-deoxy-11,12-didehydroandrographolide, andrograpanin, and flavonoids such as myricetin. Andrographolide is the single isolated principal bioactive compound responsible for much of the plant's anti-inflammatory and immunomodulatory activity. Standardized extracts are quantified by their andrographolide percentage and may offer a more consistent dose, while whole-plant extracts retain synergistic minor compounds that may contribute to overall efficacy.

### Does andrographolide interact with common medications like anticoagulants or immunosuppressants?

Andrographolide may potentiate anticoagulant effects and should be used cautiously with warfarin or similar medications due to its blood-thinning properties. It can also modulate immune function, potentially reducing the efficacy of immunosuppressive drugs used after organ transplants or for autoimmune conditions. Consult a healthcare provider before combining andrographolide with prescription medications, particularly those affecting blood clotting or immune function.

### Who benefits most from andrographolide supplementation—athletes, older adults, or people with specific conditions?

Andrographolide may benefit individuals seeking immune support, those recovering from acute infections, and people with inflammatory conditions due to its NF-κB inhibition and pro-inflammatory cytokine suppression. Older adults may benefit from its immunomodulatory effects, as it enhances IL-2 secretion and lymphocyte proliferation. However, those with autoimmune diseases should exercise caution, as enhanced immune activity could theoretically exacerbate certain conditions.

### What does clinical research show about andrographolide's effectiveness for respiratory infections and immune support?

Clinical studies demonstrate that andrographolide reduces the duration and severity of upper respiratory infections when taken prophylactically or early in infection, supported by its documented inhibition of pro-inflammatory cytokines TNF-α and IL-12. Research shows a 14% increase in lymphocyte proliferation at therapeutic concentrations, indicating immune-boosting potential, though most evidence comes from in vitro and animal models rather than large-scale human trials. The evidence is considered moderate for immune support, with stronger data available for acute respiratory illness prevention and symptom reduction.

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