# Celastrol (Tripterygium wilfordii Hook F)

**Canonical URL:** https://ingredients.hermeticasuperfoods.com/ingredients/celastrol-tripterygium-wilfordii-hook-f
**Data Source:** Hermetica Superfoods Ingredient Encyclopedia
**Updated:** 2026-04-04
**Evidence Score:** 1 / 10
**Category:** Compound
**Also Known As:** Tripterine, Celastrol (quinone methide triterpenoid), Thunder god vine triterpenoid, 2,56-dihydroxy-6-oxo-tripterine, Celastrus extract constituent

## Overview

Celastrol is a pentacyclic triterpenoid that exerts [anti-inflammatory](/ingredients/condition/inflammation) and anticancer activity by inhibiting NF-κB and AP-1 signaling, disrupting the HSP90-Cdc37 chaperone complex, inducing ROS-mediated apoptosis via peroxiredoxin inhibition, and suppressing pro-inflammatory mediators including TNF-α, IL-6, iNOS, and COX-2 at concentrations as low as 0.05–1 μM in vitro. Preclinical evidence demonstrates that celastrol induces G2/M cell cycle arrest and caspase-3/7-dependent apoptosis in hepatocellular carcinoma (Huh7) cells at concentrations above 1 μM, and exerts potent [antimicrobial](/ingredients/condition/immune-support) activity against Gram-positive bacteria with MIC values of 0.16–2.5 μg/mL, though no human clinical trials with quantified effect sizes for isolated celastrol have been published.

## Health Benefits

- **[Anti-inflammatory](/ingredients/condition/inflammation) Activity**: Celastrol suppresses nitric oxide, PGE₂, iNOS, COX-2, TNF-α, and IL-6 production at 0.05–1 μM in vitro by inhibiting NF-κB and AP-1 transcription factors, making it a multi-target anti-inflammatory agent relevant to conditions such as rheumatoid arthritis.
- **Anticancer Potential**: At concentrations above 1 μM, celastrol induces G2/M cell cycle arrest and caspase-3/7-mediated apoptosis in hepatocellular carcinoma Huh7 cells, with in vivo xenograft studies showing inhibition of tumor growth and migration when combined with phytohemagglutinin (PHA).
- **HSP90 Chaperone Inhibition**: Celastrol disrupts the HSP90-Cdc37 co-chaperone complex and binds directly to the C-terminal domain of HSP90α, causing protein oligomerization and impairing chaperone-dependent oncogenic client protein stabilization critical for tumor cell survival.
- **Antioxidant and ROS Modulation**: Celastrol and its derivatives inhibit peroxiredoxin (PRDX) enzymes, with optimized derivatives achieving IC₅₀ values as low as 0.042 μM for PRDX1, elevating intracellular [reactive oxygen species](/ingredients/condition/antioxidant) to selectively trigger apoptosis in cancer cells while protecting normal tissue at lower doses via antioxidant mechanisms.
- **Antimicrobial Activity**: Celastrol demonstrates bactericidal activity against Gram-positive bacteria such as Bacillus subtilis with MIC values of 0.16–2.5 μg/mL by disrupting the cytoplasmic membrane (inducing potassium leakage and mesosome-like structures) and rapidly inhibiting uptake of glucose, DNA, RNA, protein, and peptidoglycan precursors by more than 70% within 2–5 minutes at 3 μg/mL.
- **Neutrophil and Innate [Immune Modulation](/ingredients/condition/immune-support)**: Celastrol suppresses neutrophil oxidative burst and neutrophil extracellular trap (NET) formation, reducing citrullinated histone markers associated with NET-driven tissue damage relevant to autoimmune and inflammatory diseases.
- **SYK/MEK/ERK Pathway Suppression**: By inhibiting SYK kinase and downstream MEK/ERK signaling alongside IκBα pathway modulation, celastrol interferes with immune cell activation cascades involved in chronic inflammatory and allergic conditions at sub-micromolar concentrations.

## Mechanism of Action

Celastrol's [anti-inflammatory](/ingredients/condition/inflammation) mechanism centers on inhibition of NF-κB and AP-1 transcription factors, suppressing downstream expression of iNOS, COX-2, TNF-α, and IL-6, and blocking SYK/MEK/ERK and IκBα signaling pathways at concentrations of 0.05–1 μM. Its anticancer activity involves disruption of the HSP90-Cdc37 chaperone complex through direct binding to Cdc37 or the C-terminal domain of HSP90α, causing HSP90 oligomerization and destabilizing oncogenic client proteins, while simultaneously inducing G2/M cell cycle arrest and activating caspase-3/7-dependent apoptosis at concentrations above 1 μM. Celastrol also inhibits peroxiredoxin (PRDX) antioxidant enzymes, elevating intracellular [reactive oxygen species](/ingredients/condition/antioxidant) to pro-apoptotic levels in cancer cells, with optimized celastrol derivatives demonstrating IC₅₀ values as low as 0.042 μM for PRDX1. The compound's electrophilic quinone methide core is believed to contribute to its multi-target activity through covalent modification of reactive cysteine residues in key regulatory proteins, though this reactivity also poses selectivity and cytotoxicity challenges at higher concentrations.

## Clinical Summary

No clinical trials examining isolated celastrol as a defined intervention in human subjects have been reported in the available literature, making a formal clinical summary impossible at this time. Tripterygium wilfordii plant extracts have been used in documented clinical settings for rheumatoid arthritis and [inflammatory](/ingredients/condition/inflammation) skin diseases in China, with sex-based dosing adjustments, but these preparations contain dozens of bioactive compounds beyond celastrol, preventing attribution of outcomes to any single constituent. Preclinical xenograft data demonstrate tumor growth suppression and apoptosis induction at low concentrations in combination with phytohemagglutinin, but these findings require confirmation in dose-escalation and pharmacokinetic human studies. Confidence in celastrol's clinical utility for any specific indication is currently low, and its development as a therapeutic agent depends on overcoming bioavailability, solubility, and toxicity barriers through formulation strategies such as nanoparticle encapsulation or structural derivatization.

## Nutritional Profile

Celastrol is a purified bioactive triterpenoid compound and does not possess a conventional nutritional profile in terms of macronutrients, vitamins, or dietary minerals. Its molecular identity is defined by a pentacyclic lupane-type triterpenoid backbone with a quinone methide functional group at the A ring and a carboxylic acid at C-29, giving it a molecular weight of 450.6 g/mol and molecular formula C₂₉H₃₈O₄. Phytochemically, it is the most abundant bioactive triterpenoid in Tripterygium wilfordii root bark extracts, which also contain approximately 20 other triterpenoids, 46 diterpenoids (including the highly toxic triptolide), and 21 alkaloids. Bioavailability of celastrol is constrained by low aqueous solubility (precipitation above approximately 40 μg/mL), significant plasma protein binding, and likely extensive first-pass [metabolism](/ingredients/condition/weight-management), though precise human oral bioavailability figures have not been established.

## Dosage & Preparation

- **Purified Compound (Research Grade)**: Used exclusively in preclinical laboratory settings; dissolved in DMSO for in vitro studies at 0.05–10 μM; no pharmaceutical-grade oral formulation is commercially approved.
- **Traditional Whole-Plant Extract (Thunder God Vine)**: Root bark extracts of Tripterygium wilfordii are administered orally in traditional Chinese medicine for rheumatoid arthritis and skin diseases; doses in clinical practice are reported to be approximately one-third higher in men than women, though standardization to celastrol content is not established.
- **Effective In Vitro Concentrations**: [Anti-inflammatory](/ingredients/condition/inflammation) effects observed at 0.05–1 μM; apoptosis induction in cancer cells at >1 μM; [antimicrobial](/ingredients/condition/immune-support) bactericidal effects at 3–40 μg/mL (limited by solubility ceiling above 40 μg/mL).
- **Experimental Nanoformulations**: Celastrol has been encapsulated in lipid nanoparticles and polymeric micelles in preclinical studies to improve aqueous solubility and bioavailability, though none are approved for human use.
- **Standardization**: No commercial supplement is standardized to a defined celastrol percentage; whole-plant extracts vary widely in celastrol content depending on extraction method and plant part used.
- **Timing and Administration Notes**: No human pharmacokinetic data exist to guide dosing intervals; preclinical models suggest rapid cellular uptake, with antimicrobial inhibition occurring within 2–5 minutes of exposure at effective concentrations.

## Safety & Drug Interactions

Celastrol exhibits concentration-dependent cytotoxicity in mammalian cells, with apoptosis induction occurring above 1 μM, which presents a narrow therapeutic window that limits safe dosing and is a primary obstacle to clinical development. Tripterygium wilfordii whole-plant extracts, which contain celastrol alongside highly toxic compounds such as triptolide, carry well-documented risks of hepatotoxicity, nephrotoxicity, reproductive toxicity (including male infertility and amenorrhea), gastrointestinal disturbances, and immunosuppression, although these cannot be ascribed solely to celastrol. No specific drug interaction studies for isolated celastrol in humans have been published, but given its inhibition of [NF-κB](/ingredients/condition/inflammation), COX-2, and HSP90 pathways, theoretical interactions with immunosuppressants, NSAIDs, chemotherapy agents, and CYP450-metabolized drugs are plausible and warrant caution. Celastrol and all Tripterygium wilfordii preparations are contraindicated in pregnancy due to documented embryotoxic and teratogenic effects in animal models, and should be avoided in women of childbearing potential, patients with pre-existing hepatic or renal impairment, and individuals on concurrent immunosuppressive therapy without medical supervision.

## Scientific Research

The evidence base for celastrol is entirely preclinical, consisting of in vitro cell culture studies and in vivo rodent xenograft or [inflammation](/ingredients/condition/inflammation) models; no published randomized controlled trials isolating celastrol as a purified compound in human subjects with quantified clinical outcomes have been identified. In vitro studies have characterized concentration-response relationships in cancer cell lines (including Huh7 hepatocellular carcinoma), inflammatory macrophage and neutrophil models, and Gram-positive bacterial assays, with well-defined IC₅₀ and MIC values across multiple endpoints. Clinical use of Tripterygium wilfordii whole-plant extracts (which contain celastrol among many other constituents) has been documented in Chinese rheumatoid arthritis and skin disease populations with dose adjustments by sex, but these studies cannot be attributed to celastrol alone and generally lack the methodological rigor of controlled trials. Overall, the evidence for celastrol specifically remains at a preclinical stage, and translation to human therapeutic use requires resolution of critical challenges including poor aqueous solubility, narrow therapeutic window, and absence of validated pharmacokinetic data in humans.

## Historical & Cultural Context

Celastrol derives from Tripterygium wilfordii, a plant with a documented history in traditional Chinese medicine (TCM) spanning several centuries, where root preparations were applied to treat [inflammatory](/ingredients/condition/inflammation) arthritides, autoimmune skin disorders, and pain syndromes under TCM diagnostic frameworks. The plant is referenced in Chinese pharmacopoeial texts and was colloquially known as 'thunder god vine,' reflecting the potency and toxicity associated with its use, which demanded careful preparation and dosing by skilled practitioners. Traditional preparation involved decoction of the dried root bark or production of alcohol-based tinctures, with strict avoidance of other plant parts (leaves, flowers, stem) that carry higher acute toxicity. Modern isolation of celastrol as a discrete bioactive compound began in the mid-20th century as phytochemical fractionation techniques advanced, transitioning the compound from a component of complex herbal mixtures to a defined molecular entity of pharmacological interest.

## Synergistic Combinations

Preclinical evidence indicates that celastrol combined with phytohemagglutinin (PHA) exerts enhanced inhibition of Huh7 hepatocellular carcinoma cell growth, migration, and apoptosis induction compared to either agent alone, suggesting synergy through complementary immune-activating and direct cytotoxic mechanisms. Celastrol's inhibition of HSP90 chaperone function may potentiate the activity of kinase inhibitors or proteasome inhibitors whose oncogenic client proteins depend on HSP90 for stability, a mechanistically rational combination explored in preclinical oncology research. Its anti-[inflammatory pathway](/ingredients/condition/inflammation) targeting of NF-κB alongside COX-2 and cytokine suppression theoretically complements omega-3 fatty acids or curcumin, which also modulate eicosanoid and NF-κB pathways, though formal co-administration studies in humans have not been conducted.

## Frequently Asked Questions

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

Celastrol is a quinone methide triterpenoid compound extracted from the root bark of Tripterygium wilfordii Hook F, a plant native to China and East Asia commonly called thunder god vine. It is the most abundant and pharmacologically active triterpenoid in this plant, which also contains dozens of other bioactive diterpenoids and alkaloids. In traditional Chinese medicine, root preparations of this plant have been used for centuries to treat rheumatoid arthritis and inflammatory skin diseases.

### What are the anti-inflammatory mechanisms of celastrol?

Celastrol suppresses inflammation by inhibiting the NF-κB and AP-1 transcription factors, which reduces downstream expression of pro-inflammatory mediators including TNF-α, IL-6, iNOS, COX-2, nitric oxide, and PGE₂. It also blocks SYK kinase and downstream MEK/ERK signaling and inhibits IκBα degradation, and at 0.05–1 μM in vitro it suppresses neutrophil oxidative burst and NET formation as measured by reductions in citrullinated histones. These effects collectively make celastrol a broad-spectrum, multi-target anti-inflammatory agent in preclinical models.

### Does celastrol have anticancer properties, and what is the evidence?

Celastrol demonstrates anticancer activity in preclinical studies by inducing G2/M cell cycle arrest and caspase-3/7-dependent apoptosis in cancer cell lines such as Huh7 hepatocellular carcinoma at concentrations above 1 μM, and by inhibiting the HSP90-Cdc37 chaperone complex that stabilizes oncogenic proteins. Derivatives of celastrol inhibit peroxiredoxin 1 (PRDX1) with IC₅₀ values as low as 0.042 μM, elevating reactive oxygen species to pro-apoptotic levels in tumor cells. All current evidence is preclinical; no human clinical trials evaluating isolated celastrol for cancer have been published.

### Is celastrol safe to take as a supplement?

Isolated celastrol is not currently available as a regulated dietary supplement, and its safety in humans has not been formally established through clinical trials. At concentrations above 1 μM, celastrol induces cytotoxicity and apoptosis in mammalian cells, indicating a narrow therapeutic window. Tripterygium wilfordii plant extracts containing celastrol carry significant toxicity risks including hepatotoxicity, nephrotoxicity, male infertility, and embryotoxicity, and should only be used under medical supervision; the extracts are contraindicated in pregnancy.

### What is the difference between celastrol and triptolide?

Celastrol and triptolide are both major bioactive compounds isolated from Tripterygium wilfordii root bark, but they belong to different chemical classes: celastrol is a triterpenoid, while triptolide is a diterpenoid epoxide. Celastrol's primary targets include NF-κB, HSP90-Cdc37, and peroxiredoxins, whereas triptolide acts mainly by inhibiting RNA polymerase II-mediated transcription and is generally considered more acutely toxic with a narrower safety margin. Both compounds contribute to the observed pharmacological and toxic effects of whole Tripterygium wilfordii extracts, which is why isolated compound research is essential for separating their individual profiles.

### What dosage of celastrol from Tripterygium wilfordii is typically used in clinical research?

Most in vitro studies demonstrating anti-inflammatory effects use celastrol concentrations between 0.05–1 μM, while anticancer activity appears at concentrations above 1 μM. Human clinical trials are limited, but traditional Tripterygium wilfordii extracts have been studied at doses of 60 mg daily for rheumatoid arthritis management. The optimal human dose for isolated celastrol supplementation has not been definitively established due to limited clinical data.

### Does celastrol interact with rheumatoid arthritis medications like DMARDs or biologics?

No systematic interaction studies between celastrol and conventional DMARDs (disease-modifying antirheumatic drugs) or biologic agents have been published to date. Given that celastrol functions through NF-κB and AP-1 inhibition—similar mechanistic pathways to some biologics—concurrent use should be discussed with a healthcare provider to avoid potential redundancy or additive effects. The lack of clinical safety data makes medical supervision essential if combining celastrol with prescription rheumatoid arthritis treatments.

### What is the current evidence quality for celastrol's use in treating inflammatory conditions in humans?

The majority of evidence for celastrol's anti-inflammatory potency comes from in vitro studies and animal models showing suppression of NF-κB, AP-1, and multiple pro-inflammatory cytokines (TNF-α, IL-6, iNOS, COX-2). Human clinical trials remain scarce, with most data derived from traditional Tripterygium wilfordii extracts rather than isolated celastrol, limiting definitive efficacy claims. High-quality randomized controlled trials in humans are needed before celastrol can be recommended as a primary treatment for inflammatory disorders like rheumatoid arthritis.

---

*Source: Hermetica Superfoods Ingredient Encyclopedia — https://ingredients.hermeticasuperfoods.com*
*License: CC BY-NC-SA 4.0 — Attribution required. Commercial use: admin@hermeticasuperfoods.com*