14 Benefits of Icariin

Icariin exhibits anti-amyloid activity in many animal studies .

Beta-amyloid peptides (Aβ) are proteins that cause plaque formation and cell damage in Alzheimer’s disease .

Icariin was shown to markedly decrease β-amyloid-induced toxicity in rat adrenal embryonic cells (by inhibiting tau protein hyperphosphorylation, a key biological marker of Alzheimer’s disease ).

This is likely due to activation of the PI3K/Akt pathway, which plays a critical role in cell survival .

Icariin also exhibits protective effects against learning and memory deficiencies in animal models.

Icariin improved dementia in aluminum-intoxicated rats by reducing oxidative damage and β-amyloid deposits in the hippocampus. This is in part due to increased superoxide dismutase (SOD), an enzyme that reduces oxidative damage .

In rat models with induced brain inflammation, short-term icariin treatment was found to improve spatial learning and memory abilities. This effect is thought to be due to the lowering of pro-inflammatory cytokines (TNF-alpha and IL-B as well as COX-2, an enzyme responsible for fever, inflammation, and pain) .

Icariin can also suppress neuroinflammation by inhibiting the activation of microglia, macrophage-like cells in the brain nervous system that play a pivotal role in initiating the neuroinflammatory response .

The anti-inflammatory effect of icariin may be attributed to its inhibition of the NF-κB and p38 MAPK pathways, which are involved in microglia and proinflammatory marker activation .

Another animal study showed that icariin lessened cognitive decline by increasing BDNF and its receptor tyrosine kinase TrkB .

BDNF is a neurotrophic factor involved in cognition, synaptic plasticity, and neuronal survival .

In rats with stroke, Icariin protects against cognitive deficits by increasing acetylcholine metabolism in the hippocampus, a key neurotransmitter involved in learning and memory .

In addition, Icariin can enhance cognitive function via stimulation of the NO/cGMP pathway. Elevated levels of cGMP and nitric oxide (via icariin inhibition of PDE5) improves brain blood flow, synaptic plasticity, neurovascular dysfunction, and β-amyloid elimination from the hippocampus (memory center) and cortex.

Due to its potent anti-inflammatory, antioxidative and anti-amyloid activity in the brain, icariin may serve as a promising therapeutic option for cognitive disorders such as Alzheimer’s disease and other forms of dementia.

Icariin inhibits neurotoxicity induced by corticosterone, aluminum, hydrogen peroxide, and other toxins and promotes neuronal survival in numerous animal models .

Icariin was found to suppress neurotoxicity by maintaining intracellular calcium homeostasis in rat hippocampal neurons .

Icariin was also found to inhibit β-amyloid-induced neurotoxicity (by increasing CART (cocaine and amphetamine-regulated transcript) in cortical neuron cells). Found widely in the brain, CARTfunctions in preventing energy loss and preserving mitochondrial function .

Mitochondria are known to play a key role in increasing energy production for neuronal survival during a stroke .

Icariin also promotes neuronal survival during a stroke by increasing Sirtuin 1 (SIRT1), an enzyme that promotes cellular stress resistance.

SIRT1 activates the PGC-1alpha pathway, which is known to promote mitochondrial biogenesis and energy metabolism.

Also, SIRT1 can reduce oxidative stress, a key factor involved in protein and DNA damage in the cell.

Icariin stimulates neurogenesis by activating dormant neural stem cells in animal studies .

The HPA (hypothalamic-pituitary-adrenal) axis plays a role in mitigating physiological responses to stress, with hyperactivity implicated in depressive and anxiety disorders.

Icariin normalizes HPA axis activity (by reducing CRF and cytokines IL-6 and TNF-alpha) in CMS (chronic mild stress) rat models .

Cytokines IL-6 and TNF-alpha activate CRF, which increases HPA axis activity characterized by high levels of cortisol, a stress hormone .

Thus icariin may act as an antidepressant by decreasing HPA axis hyperactivity through inhibition of CRF and cytokine levels in depressive patients

A number of studies show that icariin enhances bone growth and repair by stimulating bone (osteoblast) (bone forming) activity and inhibiting osteoclastic (bone breakdown) activity .

Icariin increased hip and lower spine bone density in postmenopausal women by inhibiting bone destruction (bone break down) marker deoxypyridinoline and maintaining osteocalcin, a bone formation marker .

Icariin improves bone mineral density and strength in female rats with removed ovaries .

Icariin can also promote the production and activity of bone (osteoblast) cells .

Icariin stimulated the generation of cultured human bone (osteoblast) cells by increasing bone morphogenetic protein (BMP-2) production, a key protein involved in bone and cartilage formation .

Icariin was also found to enhance the production of primary osteoblasts (by increasing bone formation markers ALP, osteocalcin, COL-1 and OPG and decreasing RANKL, a protein involved in osteoclast formation) .

Icariin inhibits the formation and bone-resorbing action of osteoclasts by increasing OPG/RANKL ratios in bone cells .

Osteoprotegerin (OPG) is known to inhibit RANKL activity which plays a role in osteoclast formation and bone destruction .

In addition, Icariin can suppress osteoclast formation by decreasing superoxides, reactive oxygen species that are required for osteoclast survival and activity .

Icariin can inhibit cartilage and bone degradation in arthritic mice (by inhibiting cathepsin K, an enzyme that breaks down cartilage and bone) .

Icariin exhibits heart protective effects in many animal studies .

Icariin improved heart function and reduced tissue death in rats with an acute heart attack (myocardial infarction) by activating the PI3K-Akt pathway, which plays a critical role in cell survival .

Icariin prevented heart muscle cell death during reoxygenation following an acute heart attack by increasing Bc1-2 (an anti-cell death factor) and decreasing Bax ( a pro-cell death factor). These effects are in part due to activation of the PI3K/Akt pathway, which increases Bc1-2 in heart muscle cells .

In another study, icariin inhibited heart muscle cell death by suppressing matrix metalloproteinase (MMP) activity in rats with heart failure. MMPs are enzymes involved in heart remodeling after injury .

Icariin improved heart function by reducing oxidative damage in the mitochondria of diabetic rat hearts. Icariin improves blood flow to the heart by widening heart vessels via inhibition of Ca2+ channels, which helps reduce the risk of heart stroke and tissue death .

Hardening of arteries (atherosclerosis) is a common cause of stroke and heart attack. Icariin can reduce the risk of hardening of the arteries by lowering cholesterol levels in the blood .

Multiple studies show that icariin can promote new heart muscle cell formation by inducing cell death, increasing reactive oxygen species generation, and activating the P38 MAPK and NF-kappaB pathways in mouse embryonic stem cells, indicating that icariin may have a potential application in heart tissue engineering .

New blood vessel formation improves stroke-related tissue injuries and wound healing by increasing oxygen and nutrients to the affected area .

Icariin can stimulate blood vessel growth (by activating the MEK/ERK and PI3K/Akt/eNOS pathways) in human blood vessel cells. These pathways are associated with the generation, movement and structural shaping of blood vessel cells during blood vessel growth .

Icariin inhibits tumor formation in various types of cancer, including breast cancer, leukemia, Burkitt lymphoma, and liver cancer .

In human stomach cancer cells, icariin was able to suppress tumor cell movement and invasion (by inhibiting the Rac1-dependent VASP pathway, which is involved in cellular motility) .

Another study showed that Icariin was able to suppress the attachment and movement of stomachcancer cells (by inactivation of protein kinase A (PKA), an enzyme known to promote cell production and survival) .

Icariin inhibited human gallbladder cancer cell production and induced cell death by suppressing NF-κB activity. The NF-kB pathway plays a key role in cancer cell survival by increasing anti-cell death factors survivin and Bc1 .

Icariin triggered human liver cancer cell death (by activating the ROS/JNK-dependent mitochondrial pathway which plays a key role in initiating cell death).

Icariin was able to reduce intestinal inflammation and improve disease symptoms in mice with irritable bowel syndrome (by inhibition of STAT1 and STAT3 phosphorylation which is responsible for activating and increasing Th1 and Th17 T-cells and pro-inflammatory cytokines) .

Icariin improved airway inflammation in asthmatic rats (by adjusting the Th1/Th2 cytokine imbalance in the lung tissue). Icariin also inhibited the activation of the NF-κB pathway in lung tissue, which is involved in inflammation .

Another study showed that icariin decreased lung inflammation (by inhibiting pro-inflammatory markers TNF-α, IL-6, COX-2 and iNOS in the lung via activation of the PI3K/Akt pathway and inhibition of NF-κB) .

Icariin increases the production of toll-like receptor 9 (TLR9) in mouse macrophages. TLR9 is a protein that functions in pathogen recognition and activation of the innate immune response .

Multiple sclerosis (MS) is an autoimmune disease in which T-cells attack them in the brain nervous system (CNS), causing axon damage and disability. Icariin was found to improve disease symptoms in mice with induced MS (by suppressing the production of T cells and Th1 and Th17 cells) .

A study showed that icariin was able to reduce physical fatigue and increase endurance in mice during a weight loaded swimming test.

It was found that icariin increased blood glucose, hemoglobin and glycogen levels, factors which are known to improve speed, endurance, and exercise ability.

Icariin also decreased blood lactic acid (BLA) and blood urea nitrogen (BUN) levels indicating that icariin might reduce protein breakdown for energy and delay the buildup of lactic acid, both factors known to prevent fatigue .

Icariin protects DNA from radical-induced damage by reducing oxidative damage (through increasing SIRT1 and antioxidant enzymes CAT and Prx1) .

Icariin delays aging in mice by increasing SIRT6. SIRT6 is an enzyme that promotes DNA repair and energy metabolism and inhibits the NF-kB pathway, which is involved in cellular aging, death, and inflammation .

Icariin also delays aging in worms by promoting stress resistance, muscle function, and movement, and preventing protein build up toxicity .

A study showed that Icariin was able to inhibit Propionibacterium acnes biofilm formation in part by killing the bacterial cells. Propionibacterium acnes is a bacterium linked to the skin condition of acne, indicating that icariin may be used as a natural anti-acne drug .

In a double-blind, randomized control trial, PDE5 inhibitors can prolong the time that it takes to ejaculate .

PDE5 inhibitors enhance circadian responses to light and decrease the amount of time necessary for re-entrainment in mice.

This helps when you fly eastward. Imagine you fly east 3 time zones from California to New York.

Imagine you fly east 3 time zones from California to New York. If you normally go to sleep at 11 PM California time, then you will be going to sleep at 2 AM New York time.

If you want to go to sleep earlier, you need to wake up earlier and ‘advance’ your cycle so that you go to sleep earlier and you wake up earlier.

Icariin and PDE5 inhibitors help you advance your rhythm. See my interview with the author of this study.