triterpenes
Also known as: Triterpenoids, Pentacyclic triterpenes, α-amyrin, β-amyrin, lupeol, celastrol, Triterpenes
Overview
Triterpenes are a class of naturally occurring chemical compounds composed of three terpene units, typically C30H48 skeletons. They are found in various plants, including shea nut oil and *Tripterygium wilfordii*, and are often extracted as complex mixtures or isolated as individual compounds. These lipophilic molecules are primarily investigated for their anti-inflammatory, immunomodulatory, and potential anti-arthritic effects, with additional research exploring analgesic, anti-tumoral, and metabolic regulatory properties. Despite promising preclinical evidence, their low water solubility limits oral bioavailability, posing a challenge for therapeutic application. Research is at a moderate to advanced preclinical stage, with some early clinical studies and systematic reviews highlighting their potential, but large-scale human randomized controlled trials are still limited.
Benefits
Triterpenes exhibit significant anti-inflammatory and analgesic effects, particularly in animal models of arthritis and inflammatory pain. For instance, α-amyrin and β-amyrin have been shown to reduce mechanical and thermal hyperalgesia in rat models (p < 0.05). Celastrol, another triterpene, significantly reduced T cell counts and modulated immune cell differentiation in autoimmune arthritis models (p < 0.05). These compounds also demonstrate secondary benefits such as inhibiting serine proteases and collagenase activity, which may slow cartilage degradation in osteoarthritis. Immunomodulation occurs via shifting the Th17/Treg balance, reducing pro-inflammatory T cells, and promoting regulatory T cells. While animal models of osteoarthritis, rheumatoid arthritis, and autoimmune encephalomyelitis show consistent benefits, human data are more limited. Effect sizes in animal studies are significant, but clinical significance in humans requires further establishment. Effects are typically observed within days to weeks in animal models, suggesting chronic administration may be necessary for sustained benefits.
How it works
Triterpenes exert their effects primarily through anti-inflammatory mechanisms, involving the inhibition of pro-inflammatory cytokines and protease enzymes. They also modulate immune cell populations, specifically acting on T cells and macrophages. Key molecular targets include cannabinoid receptors CB1 and CB2, which are involved in pain and inflammation pathways. Additionally, triterpenes interact with enzymatic pathways crucial for inflammation and tissue degradation, such as serine proteases (e.g., trypsin, chymotrypsin). They can also influence transcription factors like STAT3, RORγt, and Foxp3, which regulate T cell differentiation and immune responses. However, their poor water solubility significantly limits oral bioavailability, necessitating advanced drug delivery systems to improve their pharmacokinetic profile.
Side effects
Triterpenes are generally well tolerated in preclinical studies, but human safety data are limited, and no major adverse effects have been reported at moderate doses. Common, uncommon, and rare side effects are not well characterized in humans due to insufficient clinical trials. Potential drug interactions may exist with immunosuppressants or other anti-inflammatory drugs due to overlapping mechanisms, though clinical data are currently lacking. Contraindications are not established, but caution is advised for individuals who are immunocompromised or those undergoing immune-modulating therapies. Safety data for special populations, such as pregnant or breastfeeding women and pediatric patients, are also lacking, and therefore, use in these groups is not recommended without further research.
Dosage
Optimal human dosage ranges for triterpenes are not yet established. Preclinical animal studies have utilized doses such as 30 mg/kg for α/β-amyrin and 1 mg/kg/day (intraperitoneal) for celastrol in rats. The maximum safe dose in humans is unknown, although animal toxicity studies suggest a wide margin. Due to their lipophilicity and poor oral absorption, co-administration with fats or the use of specialized delivery systems, such as nanoparticle and polymeric carrier formulations, is recommended to improve bioavailability and therapeutic efficacy. Chronic administration is likely necessary to achieve sustained anti-inflammatory effects. No specific cofactors have been identified as required for their action.
FAQs
Are triterpenes safe for long-term use?
Preclinical data suggest a favorable safety profile, but long-term human safety has not been well established due to limited clinical trials.
Can triterpenes replace conventional anti-inflammatory drugs?
Currently, triterpenes are considered adjuncts or experimental treatments; more extensive clinical trials are needed to determine if they can serve as standalone therapies.
How quickly do effects appear?
In animal studies, effects are observed within days to weeks. The timeline for human effects is currently unknown and requires further research.
Do all triterpenes have the same effects?
No, different triterpenes, such as α-amyrin, β-amyrin, lupeol, and celastrol, can vary significantly in their potency and specific mechanisms of action.
Is bioavailability a concern?
Yes, their poor water solubility significantly limits oral absorption and effectiveness, often requiring advanced delivery systems to improve bioavailability.
Research Sources
- https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0215812 – This preclinical RCT in rats demonstrated that a shea nut oil triterpene concentrate (containing α/β-amyrin and lupeol) reduced inflammatory pain and cartilage degradation in an osteoarthritis model. The study linked these effects to CB1/CB2 receptor activation and protease inhibition, providing mechanistic insights despite using a complex mixture of compounds.
- https://pmc.ncbi.nlm.nih.gov/articles/PMC8600492/ – This systematic review synthesized findings from various preclinical studies, showing that celastrol modulates immune responses by reducing T cell counts, shifting the Th17/Treg balance, and suppressing inflammatory gene expression. The review highlighted consistent findings across animal models, emphasizing celastrol's immunomodulatory potential despite limited human trial data.
- https://pmc.ncbi.nlm.nih.gov/articles/PMC10819636/ – This review focused on drug delivery systems for triterpenes, addressing their poor bioavailability. It discussed advances in nanocarrier delivery technologies aimed at improving the therapeutic outcomes of triterpenes in conditions like arthritis. The review provides a comprehensive overview of strategies to overcome pharmacokinetic challenges.
Supplements Containing triterpenes
Think Smart with Gingko Biloba
Whole Foods
ThinkSmart
Whole Foods Market
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LifeSeasons Recode With The Bredesen Protocol
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Women's Vitali-T
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Vein Formula
OL Olympian Labs
Longer Stronger Hair and Nails
Irwin Naturals
CoQ10-Plus
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CircuLegs with Horse Chestnut
Solaray
