In our daily life processes, there are many remarkable chemicals, and spermidine is one of them. It is a naturally occurring polyamine compound, widely distributed in both plants and animals. Spermidine plays an important role in human health, plant growth, and anti-aging. This article will explore the sources, distribution, functions, and potential clinical applications of spermidine. We will uncover the mysteries behind this molecule.
What is Spermidine?
Spermidine is a naturally occurring polyamine compound, derived from putrescine and is a precursor to spermine. It is a colorless liquid at room temperature, with the chemical formula C7H19N3 and a molecular weight of 145.25. Spermidine is highly soluble in water, as well as in ether and ethanol.
Spermidine is widely present in plants and animals, either in its free form or bound to fatty acids and cinnamic acid. Plants such as oats, tobacco, tomatoes, and soybeans contain high levels of spermidine. In animals, it is primarily found in organs like the heart, sperm, and eggs. Additionally, spermidine is abundant in wheat germ, corn, mushrooms (especially shiitake), blue cheese, aged cheddar cheese, milk, and some fermented foods like German sauerkraut and miso.
Spermidine plays a broad and profound role in living organisms. Animal studies show that it can extend the lifespan of yeast, worms, and fruit flies by improving autophagy. In mouse experiments, spermidine has been shown to prolong lifespan, enhance mitochondrial function in the heart, and inhibit kidney fibrosis. Human studies indicate that consuming spermidine-rich foods can lower blood pressure and reduce the risk of heart disease. Spermidine promotes cell proliferation and growth, while also enhancing DNA stability, making it valuable in biology, medicine, and agriculture.
Distribution of Spermidine
In Plants
Spermidine is widely distributed in plants, commonly found in species such as oats, tobacco, tomatoes, and soybeans. Research shows that polyamines, including spermidine and putrescine, significantly promote plant growth and development by stimulating cell division and increasing cell volume. Spermidine also delays leaf aging by reducing chlorophyll degradation and inhibits the senescence of fruits during post-harvest ripening. As spermidine and ethylene share the same precursor molecule, S-adenosylmethionine, they exhibit competitive inhibitory effects. This characteristic is one of the mechanisms through which spermidine delays plant aging. Additionally, spermidine can bind to the DNA double helix, enhancing DNA stability and improving plant resistance to heat denaturation and the effects of nucleases.
In Animals
Spermidine shows tissue-specific distribution in animals, with concentrations high in the heart, sperm, and eggs. For example, the mudskipper, a type of aquatic animal, has particularly high levels of spermidine. In humans, research has found that spermidine levels are closely linked to health conditions. Diets rich in spermidine can reduce the incidence of cardiovascular diseases, while low intake may increase the risk of stroke. Experiments have also shown that spermidine improves heart function in aging mice through mitochondrial autophagy, reducing the number of damaged mitochondria. Moreover, spermidine has demonstrated therapeutic potential in kidney fibrosis research. It may offer important insights into novel treatments for glomerular diseases.
Functions of Spermidine
Spermidine plays a vital role across biological, medical, and agricultural fields. Its main functions include:
Regulation of Reproductive and Urinary System Functions
Spermidine has an essential regulatory role in the reproductive system. It promotes sperm maturation, enhances sperm motility and vitality, and protects sperm cell membranes, boosting their antioxidant capacity. In females, spermidine helps with oocyte maturation and improves endometrial receptivity, increasing embryo implantation rates. Additionally, spermidine is used to assist in diagnosing prostate diseases. Spermidine levels in prostate fluid can serve as biomarkers for such conditions.
Antioxidant Effects and Lifespan Extension
As a natural antioxidant, spermidine delays cellular aging and protects cells from damage caused by free radicals. Research has shown that spermidine enhances autophagy, eliminating senescent cells and potentially extending lifespan. In studies, centenarians have been found to have significantly higher spermidine levels compared to older adults, further supporting its potential in anti-aging.
Inhibition of Kidney Fibrosis
Spermidine has shown remarkable effects in treating kidney fibrosis. Research indicates that spermidine inhibits the expression of EP300 protein. This activation of autophagy helps maintain the integrity of the glomerular filtration barrier. As a result, the progression of glomerular diseases is slowed.
Prevention of Age-Related Memory Decline
Spermidine’s neuroprotective effects have been confirmed in numerous studies. It improves learning and memory abilities through antioxidant and anti-inflammatory mechanisms. Some prospective studies suggest that dietary spermidine supplementation enhances cognitive function in fruit flies and mice, and may have similar effects in humans.
Detection of Spermidine
The main methods for detecting spermidine include urine spermidine detection and prostate fluid spermidine detection. These methods allow accurate measurement of spermidine levels, providing reliable data for the diagnosis and research of related diseases. Below are the details of these two detection methods and their technical processes.
1. Urine Spermidine Detection
Urine spermidine detection is conducted by collecting urine samples and analyzing them using techniques such as high-performance liquid chromatography (HPLC). The specific detection steps are as follows:
Sample Processing:
The collected urine sample is mixed with an extraction solution (acetonitrile and water mixed at a 1:1 volume ratio). The mixture is then homogenized and sonicated at 20°C for 15 minutes at 20kHz. After centrifugation, the supernatant is collected as the sample for testing.
HPLC Detection Conditions:
Instrument: Agilent 1290 Infinity Series HPLC system and Triple Quadrupole 6420 mass spectrometer from Agilent Technologies.
Chromatographic Column: Hydrophilic interaction chromatography column (100mm × 2.1mm, 5μm particle size, MS Technologies).
Mobile Phase: Acetonitrile and 0.2% formic acid water mixed at a 1:1 volume ratio, with isocratic elution.
Run Parameters: Flow rate of 0.5mL/min; injection volume of 3μL; column temperature set to 30°C; positive ion electrospray scanning mode; Multiple Reaction Monitoring (MRM) detection.
Voltage Parameters: Fragmentor voltage set to 65-75V; collision energy (CE) voltage set to 10-20eV.
Standard Curve Preparation:
Prepare spermidine standard solutions with concentrations of 50ng/mL, 200ng/mL, 400ng/mL, and 800ng/mL using acetonitrile as the solvent. Filter the solutions with a 0.22μm nylon membrane. Measure them under the same detection conditions as the urine samples. Record the peak areas. Plot the standard curve with concentration on the x-axis and peak area on the y-axis. Use the standard curve to calculate the spermidine content in the urine sample.
2. Prostate Fluid Spermidine Detection
Prostate fluid spermidine detection involves collecting prostate fluid samples. These can be obtained through prostate massage or digital rectal examination. Spermidine levels are measured using techniques such as enzyme-linked immunosorbent assay (ELISA) or high-performance liquid chromatography (HPLC). Below are the feasible detection methods:
Enzyme-Linked Immunosorbent Assay (ELISA):
ELISA is a highly sensitive method. It quickly measures spermidine concentration in prostate fluid. It relies on antigen-antibody reactions. Enzyme-catalyzed color changes are used to quantify spermidine levels.
High-Performance Liquid Chromatography (HPLC):
This method uses benzoyl chloride as a derivatization reagent. It detects spermidine through HPLC. It effectively analyzes spermidine content in prostate fluid samples with high sensitivity and accuracy.
Liquid Chromatography-Mass Spectrometry (HPLC-MS or LC-MS/MS):
HPLC combined with mass spectrometry is a modern, accurate detection method. It can detect minute changes in spermidine levels in prostate fluid. It uses high resolution and multiple reaction monitoring modes.
Reference Detection Methods:
Methods for detecting spermine and spermidine in wolfberry leaves, or measuring free putrescine, spermidine, and spermine in seawater, can provide technical guidance for spermidine measurement in prostate fluid.
Clinical Applications of Spermidine
In recent years, spermidine has gained widespread attention in clinical research and applications. Studies have confirmed that spermidine can serve as an effective preventive and therapeutic agent for prostate diseases. It also plays a significant role in improving male reproductive health. Additionally, it has shown great research potential in the fields of antioxidant activity and immune regulation.
Prostate Disease Prevention and Treatment
Spermidine regulates the cellular metabolism and immune responses in prostate tissue. It effectively reduces the production of inflammatory factors, thereby alleviating symptoms of benign prostatic hyperplasia and prostatitis. This offers new directions for the treatment of prostate-related diseases. For male reproductive health, spermidine promotes sperm maturation and motility. It improves sperm survival and fertilizing ability, opening new avenues for treating male infertility.
Antioxidant Activity
Spermidine exhibits strong antioxidant activity. It reacts with free radicals to reduce oxidative damage and promotes the expression of antioxidant enzymes. This is valuable in preventing and treating cardiovascular diseases, neurodegenerative diseases, and other conditions caused by oxidative stress.
Immune Regulation
Spermidine stimulates the secretion of growth hormones, enhancing the repair capacity of body tissues and organs. It regulates leukocyte production and accelerates the removal of reactive oxygen species, boosting the body’s resistance to viruses and diseases. For example, in the treatment of immune diseases like psoriasis, spermidine acts as an immune regulator. It can effectively suppress overactive immune responses, relieve inflammation, and show promising therapeutic potential.
Myocardial Infarction and Liver Protection
In the treatment of myocardial infarction, spermidine regulates myocardial cell energy metabolism. It reduces oxidative stress and inflammation, promoting the repair and regeneration of myocardial cells. For liver protection, it inhibits inflammation and oxidative damage. This is helpful to maintain normal liver function.
Precautions for Spermidine
Spermidine may have skin corrosive effects and can cause severe eye damage. The need for supplemental spermidine and its potential benefits for diseases have not been confirmed by clinical trials. In the absence of relevant clinical research, it is advised that individuals exercise caution regarding spermidine supplementation.
Excessive intake of spermidine may harm the body. Some individuals may experience symptoms such as dizziness, headache, stomach pain, nausea, and indigestion. In more severe cases, side effects may include vomiting, dizziness, blurred vision, and persistent hair loss. Spermidine may also affect liver and kidney functions, increasing the risk of kidney disease, cardiovascular disease, and neurological disorders. Children, pregnant women, the elderly, and individuals with weakened immune systems are more susceptible to the effects of spermidine.
Conclusion
Spermidine is a remarkable polyamine compound that has garnered significant attention for its wide applications in biology, medicine, and agriculture. From extending lifespan to improving cognitive function, and from regulating plant growth to inhibiting kidney fibrosis, spermidine demonstrates incredible potential. As research continues, spermidine may provide more solutions for human health and agricultural development, becoming an important breakthrough in the field of life sciences.
