# Matrine (Sophora flavescens alkaloid)

**Canonical URL:** https://ingredients.hermeticasuperfoods.com/ingredients/matrine-sophora-flavescens-alkaloid
**Data Source:** Hermetica Superfoods Ingredient Encyclopedia
**Updated:** 2026-04-04
**Evidence Score:** 1 / 10
**Category:** Compound
**Also Known As:** Matrine (C₁₅H₂₄N₂O), (+)-Matrine, Ku Shen alkaloid, Sophora alkaloid matrine, CAS 519-02-8

## Overview

Matrine (C₁₅H₂₄N₂O, MW 248.36 g/mol) is a quinolizidine alkaloid that exerts antitumor effects by inhibiting PI3K/AKT/mTOR signaling, suppressing NF-κB and MAPK [inflammatory](/ingredients/condition/inflammation) cascades, and modulating microRNA expression to downregulate oncogenic targets including EGFR, Bcl-2, and Wnt/β-catenin. In preclinical cell models, matrine reduced IL-6 to 82.14 ± 5.75% and TNF-α to 73.01 ± 1.56% of LPS-stimulated control levels in RAW 264.7 macrophages, while demonstrating concentration- and time-dependent proliferation inhibition across hepatoma, lung, and breast cancer cell lines.

## Health Benefits

- **Anticancer Activity**: Matrine inhibits proliferation and induces apoptosis in hepatoma cells (HepG2, Huh7, Bel-7402) by suppressing PI3K/AKT/mTOR signaling, reducing stem cell markers CD90, CD133, and EpCAM, and lowering the Bcl-2/Bax ratio to favor programmed cell death.
- **Anti-inflammatory Effects**: By inhibiting NF-κB nuclear translocation and suppressing MAPK and JAK/STAT signaling cascades, matrine significantly reduces [pro-inflammatory cytokine](/ingredients/condition/inflammation) production, including decreasing IL-6 and TNF-α output in LPS-stimulated macrophages to approximately 82% and 73% of untreated model levels, respectively.
- **Cardiovascular Protection**: Matrine exerts cardioprotective effects by downregulating Akt phosphorylation at Thr495, upregulating endothelial nitric oxide synthase (eNOS) activity and GSK-3β phosphorylation, and reducing DDAH2 expression, collectively improving [endothelial function](/ingredients/condition/heart-health) and reducing oxidative vascular stress.
- **Antiviral and Antibacterial Properties**: Matrine demonstrates direct [antimicrobial](/ingredients/condition/immune-support) activity with minimum inhibitory concentrations of 12.5 mg/mL against Escherichia coli and 25 mg/mL against Staphylococcus aureus, while synthetic derivatives exhibit markedly enhanced potency, achieving 60–70% mosquito larvicidal activity at concentrations as low as 1 μg/mL.
- **[Neuroprotective Effect](/ingredients/condition/cognitive)s**: Preclinical data indicate matrine attenuates neuroinflammatory cascades by suppressing glial NF-κB activation and reducing neurotoxic cytokine release, suggesting potential utility in inflammatory neurodegenerative conditions, though human evidence remains absent.
- **Antioxidant Activity**: Matrine scavenges [reactive oxygen species](/ingredients/condition/antioxidant) and upregulates endogenous antioxidant pathways, partially through eNOS activation and GSK-3β modulation, reducing oxidative damage in cardiac and hepatic cell models.
- **Lung Cancer Suppression via miRNA Modulation**: In NCI-H1299 non-small cell lung cancer cells, matrine upregulates miR-133a expression, which subsequently inhibits the EGFR/AKT/MMP-9 axis, reducing both tumor cell proliferation and invasive metastatic potential in vitro.

## Mechanism of Action

Matrine operates through pleiotropic molecular mechanisms centered on the suppression of oncogenic and inflammatory signaling networks. In hepatocellular carcinoma models, it inhibits the PI3K/AKT/mTOR pathway to reduce survival signaling, downregulates surface stem-cell markers (CD90, CD133, EpCAM, CCR7), and suppresses TMEM16A chloride channel expression while normalizing the Bcl-2/Bax apoptotic ratio. In breast cancer cells (MCF-7, T47D), matrine downregulates oncogenic miR-21 to derepress the tumor suppressor PTEN, leading to AKT dephosphorylation; it also suppresses LIN28A, allowing let-7b accumulation that in turn inhibits Wnt/β-catenin signaling and reduces cyclin D1 (CCND1) expression to arrest cell cycle progression. Anti-inflammatory activity is mediated through concurrent inhibition of NF-κB nuclear translocation, attenuation of p38 MAPK and ERK phosphorylation, and suppression of JAK2/STAT3 activation, reducing transcription of [pro-inflammatory cytokine](/ingredients/condition/inflammation) genes including IL-6, TNF-α, and IL-1β.

## Clinical Summary

No human clinical trials with reported sample sizes, effect sizes, or controlled designs were identified for matrine as an isolated compound in the current literature. Matrine-containing traditional Chinese medicine formulations (e.g., Sophora flavescens root preparations) have historical use in clinical settings in China, particularly in oncology supportive care, but standardized outcome data from these applications are not consistently published in internationally indexed journals. Preclinical in vivo rodent studies support [anti-inflammatory](/ingredients/condition/inflammation) and antitumor activity, but species-specific pharmacokinetics, maximum tolerated doses in humans, and human bioavailability data have not been formally characterized in registerable trial formats. Confidence in matrine's clinical efficacy for any specific indication must therefore remain low until prospective, controlled human studies are completed.

## Nutritional Profile

Matrine is a pure alkaloid compound (C₁₅H₂₄N₂O) and does not constitute a nutritional ingredient with macronutrient or micronutrient contributions. As a low-molecular-weight (248.36 g/mol) bicyclic nitrogen-containing organic compound, it belongs to the quinolizidine alkaloid class alongside structurally related compounds oxymatrine, sophoridine, and sophocarpine, which co-occur in Sophora flavescens root extracts. Bioavailability of matrine following oral administration is influenced by first-pass hepatic [metabolism](/ingredients/condition/weight-management); preclinical rodent studies suggest moderate oral absorption, but human bioavailability data, plasma half-life, and protein binding parameters have not been formally established in published pharmacokinetic studies. The compound is soluble in water and common organic solvents, facilitating both aqueous traditional decoction extraction and modern organic solvent-based isolation techniques.

## Dosage & Preparation

- **Pure Alkaloid Extract (Research Grade)**: Used in experimental concentrations ranging from 0.1–2.0 mg/mL in cell assays; no standardized human supplemental dose has been established from clinical trials.
- **Sophora flavescens Root Powder/Decoction (Traditional)**: Typically prepared as a water decoction of 3–9 g of dried root per day in traditional Chinese medicine practice, though matrine content varies significantly by extraction method and plant material quality.
- **Standardized Matrine Extract Capsules**: Available in some Asian herbal supplement markets at concentrations of 98% matrine purity, but no clinically validated dose range exists for human use; empirical traditional dosing is not directly translatable to isolated alkaloid doses.
- **Injectable Matrine Formulations**: Used in some Chinese clinical oncology settings as adjunctive therapy (e.g., matrine injection), with doses typically guided by institutional protocols rather than peer-reviewed trial consensus.
- **Timing Notes**: Animal studies administer matrine daily without specific circadian timing requirements; absence of human pharmacokinetic data precludes evidence-based timing recommendations.
- **Standardization Benchmark**: Research-grade extracts are standardized to ≥98% matrine by HPLC; commercial herbal products referencing Sophora flavescens extract are inconsistently standardized and may not declare matrine content.

## Safety & Drug Interactions

Matrine is characterized in preclinical literature as a relatively low-toxicity alkaloid with fewer adverse effects than crude Sophora flavescens whole-root extracts, though formal human toxicology studies establishing no-observed-adverse-effect levels (NOAELs) or maximum tolerated doses in humans are not available in the published literature. In animal models, high-dose matrine administration has been associated with neuromuscular effects consistent with nicotinic [acetylcholine](/ingredients/condition/cognitive) receptor modulation (a property shared by quinolizidine alkaloids as a class), suggesting potential for dose-dependent nervous system side effects at supratherapeutic concentrations. Potential drug interactions have not been systematically characterized in humans; based on its modulation of CYP enzyme substrates and PI3K/AKT pathway components, caution is theoretically warranted when co-administered with immunosuppressants, chemotherapeutic PI3K inhibitors, anticoagulants, or [cardiovascular](/ingredients/condition/heart-health) medications affecting nitric oxide signaling. Pregnancy and lactation safety data are absent, and given the compound's potent cell-cycle-modulating and [cytokine](/ingredients/condition/inflammation)-suppressing properties, use during pregnancy or breastfeeding should be strictly avoided pending evidence-based guidance.

## Scientific Research

The preponderance of matrine research consists of in vitro cell line studies and rodent in vivo models, with no published Phase I–III randomized controlled trials identified in the peer-reviewed literature to date. Preclinical evidence is mechanistically detailed and reproducible across multiple cancer cell lines, including hepatoma (HepG2, Huh7, Bel-7402), colorectal (RKO), lung (NCI-H1299), and breast (MCF-7, T47D) models, with quantified survival rates such as 86.6 ± 2.6% cell viability in Bel-7402 at tested concentrations, demonstrating concentration- and time-dependent antiproliferative effects. [Anti-inflammatory](/ingredients/condition/inflammation) studies in LPS-stimulated RAW 264.7 macrophages provide specific cytokine reduction data (IL-6: 82.14 ± 5.75%; TNF-α: 73.01 ± 1.56% of model group), lending reproducible quantitative benchmarks, though translation to human pharmacodynamics remains unvalidated. The overall evidence base is classified as preliminary-to-moderate in strength; while the mechanistic breadth and preclinical consistency are promising, the complete absence of registered human clinical trial data necessitates cautious interpretation of any therapeutic claims.

## Historical & Cultural Context

Sophora flavescens root (Ku Shen, meaning 'bitter ginseng') has been used in traditional Chinese medicine for over two millennia, documented in classical texts including the Shennong Bencao Jing (Divine Farmer's Materia Medica), where it was prescribed for conditions including dysentery, jaundice, skin inflammatory disorders, and parasitic infections. The alkaloid matrine was first chemically isolated by Japanese pharmacognosist Nagai in the late 19th century, representing one of the early phytochemical characterizations of Asian medicinal plant alkaloids. In Traditional Chinese Medicine, Ku Shen root decoctions were prepared by boiling dried root slices and administered orally or applied topically for eczema, leprosy-like skin conditions, and vaginal inflammatory conditions, reflecting the compound's recognized [antimicrobial](/ingredients/condition/immune-support) and [anti-inflammatory](/ingredients/condition/inflammation) properties. Matrine's modern pharmacological investigation expanded significantly from the 1980s onward, particularly in China, where it became a subject of intensive anticancer research and is incorporated into some registered Chinese proprietary medicines used in oncology supportive care.

## Synergistic Combinations

Matrine's inhibition of the PI3K/AKT/mTOR pathway suggests potential additive or synergistic effects when combined with mTOR inhibitors (e.g., rapamycin analogues) or EGFR inhibitors used in oncology, as matrine simultaneously suppresses upstream receptor expression and downstream survival signaling through complementary nodes. In traditional Chinese medicine formulations, Sophora flavescens is frequently combined with Phellodendron amurense (Huang Bai) and Cnidium monnieri for enhanced [antimicrobial](/ingredients/condition/immune-support) and anti-inflammatory effects, a combination that may produce additive NF-κB suppression through distinct alkaloid classes acting on overlapping [inflammatory pathway](/ingredients/condition/inflammation)s. Preclinical data also suggest that matrine's upregulation of PTEN and suppression of Wnt/β-catenin in breast cancer cells could be complemented by curcumin's independent downregulation of the same pathway, making a matrine-curcumin combination a theoretically rational but experimentally unvalidated anti-proliferative pairing.

## Frequently Asked Questions

### What is matrine and where does it come from?

Matrine is a tetracyclic quinolizidine alkaloid (C₁₅H₂₄N₂O, molecular weight 248.36 g/mol) extracted primarily from the roots of Sophora flavescens (Ku Shen), a medicinal shrub used in traditional Chinese medicine for over two thousand years. It is also found in Sophora alopecuroides and other Sophora species native to China, Japan, Korea, and Central Asia. The compound was first isolated chemically by Japanese researcher Nagai in the late 19th century and has since become one of the most studied alkaloids in Chinese pharmacognosy.

### What are the proven anticancer effects of matrine?

Matrine demonstrates significant anticancer activity in multiple preclinical cell line models, including hepatoma (HepG2, Huh7, Bel-7402), colorectal (RKO), lung (NCI-H1299), and breast cancer (MCF-7, T47D) cells, primarily by inhibiting the PI3K/AKT/mTOR signaling pathway and modulating microRNA expression. In breast cancer cells, it downregulates miR-21 to restore PTEN tumor suppressor function and suppresses LIN28A to allow let-7b-mediated inhibition of Wnt/β-catenin and cyclin D1. However, no human clinical trials have confirmed these anticancer effects, so all current evidence remains at the preclinical stage.

### How does matrine reduce inflammation at the molecular level?

Matrine suppresses inflammation through three primary molecular mechanisms: inhibition of NF-κB nuclear translocation (preventing transcription of inflammatory cytokine genes), attenuation of MAPK signaling (reducing p38 and ERK phosphorylation), and suppression of the JAK2/STAT3 pathway. In LPS-stimulated RAW 264.7 macrophage experiments, these combined actions reduced IL-6 levels to 82.14 ± 5.75% and TNF-α levels to 73.01 ± 1.56% of untreated model group values. This multi-target anti-inflammatory profile distinguishes matrine from single-pathway anti-inflammatory agents.

### Is matrine safe to take as a supplement, and are there drug interactions?

Matrine is characterized in preclinical research as relatively low-toxicity compared to crude Sophora flavescens extract, but formal human safety studies establishing safe dose ranges, NOAELs, or drug interaction profiles have not been published. As a quinolizidine alkaloid class compound, high doses may interact with nicotinic acetylcholine receptors, potentially causing neuromuscular effects, and theoretical interactions exist with PI3K inhibitors, immunosuppressants, and cardiovascular drugs affecting nitric oxide signaling. Pregnancy and lactation safety are completely unestablished, and use should be avoided in these populations until evidence-based guidance is available.

### What is the recommended dosage of matrine for humans?

No standardized, clinically validated human dosage for isolated matrine has been established through published Phase I–III clinical trials. Traditional Chinese medicine uses Sophora flavescens root decoctions at approximately 3–9 g of dried root per day, but the matrine content of these preparations varies substantially by extraction method and plant source quality. Research-grade matrine is studied at experimental concentrations of 0.1–2.0 mg/mL in cell assays, and injectable matrine formulations used in some Chinese oncology settings are dosed according to institutional protocols not derived from international trial consensus.

### Which forms of matrine are available as supplements, and which has the best absorption?

Matrine is available as standardized alkaloid extracts from Sophora flavescens root, with most commercial supplements offering 95–98% pure matrine in capsule or powder form. Standardized extracts demonstrate superior bioavailability compared to whole plant material due to concentrated alkaloid content and enhanced gastrointestinal absorption. Liposomal or nano-formulated matrine variants may offer improved cellular uptake, though clinical evidence comparing delivery methods remains limited.

### What clinical research evidence exists for matrine's effectiveness in human trials?

Most matrine evidence derives from in vitro and animal studies demonstrating significant antiproliferative and anti-inflammatory effects; however, well-designed human clinical trials remain scarce, particularly for cancer applications. Published human research is predominantly from China and Asia, with limited Phase 2 or 3 trials meeting Western regulatory standards. Current evidence supports further investigation but warrants caution against overstating efficacy claims pending larger, controlled human studies.

### Who should avoid matrine supplementation, and are there specific populations at higher risk?

Pregnant and nursing women should avoid matrine due to limited safety data and potential alkaloid effects on fetal development; individuals with liver disease should use caution given hepatic metabolism pathways. Patients undergoing chemotherapy or immunosuppressive therapy should consult healthcare providers before combining matrine, as its apoptosis-inducing mechanisms may create unpredictable interactions with pharmaceuticals. Children and individuals with hypersensitivity to Sophora alkaloids represent additional at-risk groups requiring medical supervision.

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