Rutacaerpine
Also known as: Rutaecarpine, 8,13-dihydroindolo[2′,3′:3,4]pyrido[2,1-b]quinazolin-5(7H)-one
Overview
Rutaecarpine is a major indole alkaloid isolated from the fruit of Evodia rutaecarpa (also known as Tetradium ruticarpum), a plant traditionally used in Chinese medicine. It is currently being investigated for its potential cardiovascular protective, anti-inflammatory, and osteoblastic differentiation effects, as well as its possible role in treating benign prostatic hyperplasia (BPH). This compound exhibits multi-target pharmacological activities, including the upregulation of cholesterol transporter ABCA1, modulation of signaling pathways related to bone formation, and inhibition of androgen receptor signaling. While promising, research on rutaecarpine is still emerging, with most studies conducted in vitro and in animal models. There is a notable lack of high-quality randomized controlled trials (RCTs) in humans, meaning its efficacy and safety in human populations are not yet well-established.
Benefits
Rutaecarpine has demonstrated several potential benefits in preclinical studies. It enhances osteoblastic differentiation and bone formation by activating focal adhesion kinase (FAK), ERK, and TGFβ pathways in human bone marrow stromal cells, suggesting a role in bone health. It also upregulates ABCA1 expression, promoting cholesterol efflux and reducing atherosclerosis in ApoE knockout mice, indicating significant cardiovascular protective potential. Furthermore, rutaecarpine has been shown to attenuate testosterone-induced benign prostatic hyperplasia in rats by inhibiting 5α-reductase and androgen receptor signaling. Secondary effects observed in preclinical studies include anti-inflammatory and antithrombotic activities. While these findings are promising, they are primarily derived from cell and animal models, and no human clinical data is available to confirm these benefits or their clinical significance in humans.
How it works
Rutaecarpine exerts its effects through several molecular mechanisms. In bone health, it activates key signaling pathways such as FAK, ERK, and SMAD2, which are crucial for promoting osteogenesis. For cardiovascular protection, it upregulates ATP-binding cassette transporter A1 (ABCA1), a protein essential for reverse cholesterol transport, thereby enhancing cholesterol efflux. In the context of benign prostatic hyperplasia, rutaecarpine inhibits the 5α-reductase enzyme and modulates androgen receptor signaling, which are critical pathways involved in androgen-driven prostate growth. Overall, rutaecarpine interacts with the skeletal system cells, influences lipid metabolism within the cardiovascular system, and modulates endocrine pathways related to androgens.
Side effects
The safety profile of rutaecarpine is not well-established, with limited human data available. Preclinical studies suggest potential cardiotoxicity, particularly at high doses or with overdose of Evodia extracts containing rutaecarpine. While common side effects are not well-documented in humans, in vitro studies indicate potential cytotoxicity at high concentrations. Rare but serious side effects, such as cardiotoxicity, have been linked to overdose or unsuitable use in animal models. Drug interactions are largely unknown, but caution is advised due to its reported effects on cytochrome P450 enzymes and the cardiovascular system. Contraindications are not formally established, but individuals with pre-existing cardiovascular conditions should exercise caution due to the potential for toxicity at higher doses. There is no data available regarding its safety during pregnancy, lactation, or for pediatric use.
Dosage
The minimum effective dose of rutaecarpine in humans has not been established. In vitro studies have shown effective concentrations, such as 0.27 μM for ABCA1 upregulation, but these do not directly translate to human oral dosages. Optimal dosage ranges for humans are unknown, and animal studies utilize variable dosing regimens. Crucially, the maximum safe dose has not been defined, and overdose in animal studies has been linked to cardiotoxicity. Timing considerations are also limited; osteogenic effects in vitro were observed after 21 days. Rutaecarpine has typically been studied as a purified compound or within plant extracts, highlighting the need for standardization if used therapeutically. Factors affecting its absorption and bioavailability in humans are not yet characterized.
FAQs
Is rutaecarpine safe?
The safety profile of rutaecarpine is not fully established in humans. Preclinical studies suggest potential cardiotoxicity at high doses, indicating that caution is warranted. More research is needed to determine its safety for human consumption.
What conditions might benefit from rutaecarpine?
Preclinical evidence suggests potential benefits for conditions such as osteoporosis, atherosclerosis, and benign prostatic hyperplasia (BPH). However, these findings are from animal and cell studies, and human clinical data is lacking.
Are there human clinical trials?
As of now, there are no high-quality randomized controlled trials (RCTs) in humans identified for rutaecarpine. Most research has been conducted in laboratory settings or animal models.
How long does it take to see effects?
In vitro studies on osteogenic effects suggest a timeframe of about three weeks. Animal models indicate chronic effects observed over weeks to months, but human response times are unknown.
Is it better as isolated compound or plant extract?
Most research has used isolated rutaecarpine. Plant extracts contain multiple compounds, which could influence efficacy and safety differently than the isolated compound, requiring further investigation.
Research Sources
- https://pmc.ncbi.nlm.nih.gov/articles/PMC11024792/ – This in vitro study investigated rutaecarpine's effects on human bone marrow stromal cells. It found that rutaecarpine upregulated osteoblastic differentiation genes and activated FAK, ERK, and SMAD2 pathways, suggesting its potential for bone formation. The study provides high-quality mechanistic insights but is limited to cell culture.
- https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.1028046/full – This study, involving in vivo and in vitro toxicity assessments, found that high doses of rutaecarpine-containing extracts caused cardiotoxicity and cytotoxicity in rat cardiomyocytes and rats. It highlights an important safety signal for rutaecarpine, indicating potential adverse effects at elevated concentrations, though its relevance to typical human dosing remains unclear.
- https://pmc.ncbi.nlm.nih.gov/articles/PMC4137366/ – This animal study using ApoE knockout mice demonstrated that rutaecarpine upregulated ABCA1 expression, reduced atherosclerosis, and exhibited cardiovascular protective effects. It provides good preclinical evidence supporting a mechanism for cardiovascular benefits, but is limited by being an animal model with a small sample size.
- https://www.jomh.org/articles/10.22514/jomh.2024.183 – This animal study investigated rutaecarpine's effect on testosterone-induced benign prostatic hyperplasia (BPH) in rats. It found that rutaecarpine inhibited 5α-reductase activity and androgen receptor signaling, leading to a reduction in prostate enlargement. This provides relevant preclinical data for BPH, but human validation is needed.