ACB: PI3K/AKT/mTOR/Sonic Hedgehog Pathway Inhibitor

“For most of the twentieth century, there was a general consensus that brain cells could not renew themselves once the developmental period was over. Then, especially over the last two decades, overwhelming evidence gradually accumulated for the capacity of new neurons to be born in the adult brain in two clearly defined locations: the subventricular zone and the dentate gyrus (DG) of the hippocampus. The hippocampus is well known to play important roles in learning and memory, and this adult DG neurogenesis has not only been implicated in memory but has led to ideas that it could be harnessed to treat neurodegenerative and neuropsychiatric disorders.”

https://www.tandfonline.com/doi/full/10.1517/13543770902721279?scroll=top&needAccess=true

Plant compound found in spices, herbs increases brain connections

Flavonoid apigenin has potential to treat diseases like schizophrenia, depression, Alzheimer’s and Parkinson’s

“Apigenin, a substance found in parsley, thyme, chamomile and red pepper, improves neuron formation and strengthens the connections between brain cells, new lab research demonstrates.”

New approach in treatment of brain injury: Neurotrophic effects of Apigenin

“Brain injury initiates a neuroinflammatory cascade that contributes to substantial neuronal damage. Administration of lipopolysaccharide (LPS) impaired antioxidant mechanisms, increased peroxidation and impaired mitochondrial redox activity causing brain inflammation as well as neuronal damage and impairment of brain monoamines. Apigenin gathered extensive attention in recent years because of its chemopreventive, antioxidant and antiinflammatory effects. This study aimed to evaluate the impact of apigenin in LPS induced brain injury in experimental rats and to evaluate its role in monoamines regulation as well as DNA damage reduction. Forty male albino rats were used in this study, divided into four groups (control, apigenin, LPS and treated groups). Brain malondialdehyde (MDA), brain nitric oxide (NO) and serum paraoxnase activity (PON-1) were estimated colorimeterically. DNA damage was evaluated by comet assay method, in addition to brain monoamines assessment by HPLC. Histopathological and Immunohistochemistry of cyclooxygenases (COX-1, COX-2) were also performed. The data showed that lipopolysaccharide significantly increased brain MDA, NO and monoamines concomitant with a reduction in PON-1. Contrarily, apigenin supplementation improved these values in treated group. The present study provides insights into the design of flavonoid with optimal neuroprotective activities.”

POTENT SASP INHIBITOR

During senescence, cells express molecules called senescence-associated secretory phenotype (SASP), including growth factors, proinflammatory cytokines, chemokines, and proteases. The SASP induces a chronic low-grade inflammation adjacent to cells and tissues, leading to degenerative diseases. The anti- inflammatory activity of flavonoids was investigated on SASP expression in senescent fibroblasts. Effects of flavonoids on SASP expression such as IL-1a, IL-1b, IL-6, IL-8, GM-CSF, CXCL1, MCP-2 and MMP-3 and signaling molecules were examined in bleomycin-induced senescent BJ cells. In vivo activity of apigenin on SASP suppression was identified in the kidney of aged rats. Among the five naturally-occurring flavonoids initially tested, apigenin and kaempferol strongly inhibited the expression of SASP. These flavonoids inhibited NF-kB p65 activity via the IRAK1/IkBa signaling pathway and expression of IkBz. Blocking IkBz expression especially reduced the expression of SASP. A structure-activity relationship study using some synthetic flavones demonstrated that hydroxyl substitutions at C-20,30,40,5 and 7 were important in inhibiting SASP production. Finally, these results were verified by results showing that the oral administration of apigenin significantly reduced elevated levels of SASP and IkBz mRNA in the kidneys of aged rats. This study is the first to show that certain flavonoids are inhibitors of SASP production, partially related to NF-kB p65 and IkBz signaling pathway, and may effectively protect or alleviate chronic low-grade inflammation in degenerative diseases such as cardiovascular diseases and late-stage cancer. Inhibitory activity of apigenin on IL-6, IL-8, and IL-1b was the most potent among the five flavonoids that were tested (86.5%, 60.9%, and 94.9% at 10 mM, respectively).

Apigenin and preventing/reversing alcohol liver injury.

“In conclusion, our present results demonstrate that apigenin can exert an inhibitory effect on ethanol-induced oxidative stress and LPS-induced inflammatory response in the cultured BRL cells, and its mechanisms may be related to the reduction of CYP2E1 expression, increment of antioxidant ability, and regulation of inflammatory gene expression. These effects of apigenin may be good for the prevention and treatment of alcoholic liver injury.”

https://www.sciencedirect.com/science/article/pii/S1214021X1730162X

You want high NAD+ levels. ( CD38 is a key enzyme involved in the degradation of NAD+) Apigenin blocks CD38.

Flavonoid apigenin is an inhibitor of the NAD+ ase CD38: implications for cellular NAD+ metabolism, protein acetylation, and treatment of metabolic syndrome

“Metabolic syndrome is a growing health problem worldwide. It is therefore imperative to develop new strategies to treat this pathology. In the past years, the manipulation of NAD+ metabolism has emerged as a plausible strategy to ameliorate metabolic syndrome. In particular, an increase in cellular NAD+ levels has beneficial effects, likely because of the activation of sirtuins. Previously, we reported that CD38 is the primary NAD+ase in mammals. Moreover, CD38 knockout mice have higher NAD+ levels and are protected against obesity and metabolic syndrome. Here, we show that CD38 regulates global protein acetylation through changes in NAD+ levels and sirtuin activity. In addition, we characterize two CD38 inhibitors: quercetin and apigenin. We show that pharmacological inhibition of CD38 results in higher intracellular NAD+ levels and that treatment of cell cultures with apigenin decreases global acetylation as well as the acetylation of p53 and RelA-p65. Finally, apigenin administration to obese mice increases NAD+ levels, decreases global protein acetylation, and improves several aspects of glucose and lipid homeostasis.”

http://diabetes.diabetesjournals.org/content/early/2012/11/18/db12-1139.short

“Scientists are discovering new ways that NAD+ facilitates healthy longevity.

NAD+ levels markedly decline with age, creating an energy deficit that decreases the body’s ability to retain youthful function.

To give you an idea how impactful NAD+ can be, by age 50 a typical person may have only half the NAD+ they did in youth. By age 80, NAD+ levels drop to only 1% to 10% expressed in youth.

Deficiency of NAD+ predisposes us to accelerated aging and impedes our ability to fully benefit from resveratrol.

http://www.lifeextension.com/Magazine/2018/2/Anti-Aging-Effects-Of-NAD/Page-01

Apigenin prevents age related testosterone decline.

(APIGENIN) : Decreases COX2 while increasing StAR thus suppressing age related testosterone decline.
“During the course of male aging, circulating levels of testosterone decline [1, 2], resulting in decreases in muscle function, bone density, sex function and other physiological functions [3-5]. It was also observed that serum testosterone concentrations were significantly lower in men with Alzheimer’s disease in comparison to non-demented and age-matched men [6, 7]. Supplementation with testosterone reduced β-amyloid peptide and hyperphosphorylation of τ protein, two bio-markers of the disease [8-10]. The studies suggested that low blood testosterone is a possible risk factor for development of Alzheimer’s disease [11]. To improve the health of aging males, especially those suffering from age-associated hypogonadism, we have been attempting to determine if it is possible to delay the age-related decline in blood testosterone concentration.

Testosterone is mainly synthesized in testicular Leydig cells from substrate cholesterol and then released into the circulation [12]. It is known that the levels of blood testosterone are affected by multiple physiological and biochemical factors associated with aging [13]. It has also been shown that the primary site for the decline in blood testosterone appears to be at the level of testosterone biosynthesis in aging Leydig cells [14]. The rate-limiting step in testosterone biosynthesis is the transfer of the substrate cholesterol from the outer to the inner mitochondrial membrane to initiate the steroidogenic process [15]. Previous studies reported that a newly synthesized protein induced by trophic hormone, namely the steroidogenic acute regulatory (StAR) protein, plays a critical function at this step by facilitating the mitochondrial cholesterol transfer [16-18]. A large body of evidence demonstrated that the levels of StAR protein expression strongly affect testosterone production in Leydig cells [19]. However, StAR protein expression also decreases during the course of Leydig cell aging, and the cholesterol supply to the mitochondrial inner membrane is reduced in aged Leydig cells [20-22]. These studies implicated the involvement of an age-related decline in StAR gene expression in the decrease in testosterone production.

In addition, our studies have demonstrated that expression of cyclooxygenase-2 (COX2, an isoform of cyclooxygenase) increases during Leydig cell aging, a process that enhances the COX2-dependent inhibition of StAR gene expression. Consequently, the age-related increase in COX2 results in decreases in StAR gene expression and testosterone biosynthesis. When COX2 activity was inhibited, StAR protein expression and testosterone production were increased. Moreover, feeding aged rats with a selective COX2 inhibitor reversed the decreased StAR protein and blood testosterone concentration [23, 24].

Further studies showed that the observed COX2-dependent inhibition of StAR gene expression involves the negative signaling through an autocrine loop consisting of COX2-thromboxane A synthase (TBXAS)-thromboxane A2 (TBX A2)-receptor, in which TBX A2 generated by the co-action of COX2 and TBXAS is released from Leydig cells, and then binds to its receptors [25, 26]. These studies further indicated that the TBX A2-receptor complex regulate the expression or stability of DAX-1 (dosage sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome, gene-1) protein, a transcriptional repressor of StAR gene expression. Blocking the COX2-dependent signaling through this loop reduced DAX-1 protein and increased the sensitivity of Leydig cells to trophic hormone stimulation, resulting in dramatic increases in StAR gene expression and testosterone production in aged Leydig cells. These studies suggested that it is possible to delay the age-related decline in testosterone production by interrupting the signaling through this loop at any step, by either inhibiting the activity of COX2 or TBXAS, or by blocking the TBX A2 receptor.

We have continued the studies in an attempt to identify natural compounds in food or food supplements that could enhance StAR gene expression in Leydig cells by intervention in the mechanism.
After screening a group of compounds, the present study identified a natural flavonoid, apigenin that interrupted the COX2-dependent signaling by blocking the TBX A2 receptor and increased StAR gene expression and steroidogenesis in mouse Leydig cells.”

Apigenin as an Anti-Aging Skin Treatment

Skin aging is a complex biological process prematurely induced by innate and external factors. We evaluated the anti-aging effects of apigenin, a plant flavone, on human skin exposed to ultraviolet radiation. A total of 25 female subjects applied a 10% apigenin- containing regimen (eye cream, moisturizer, and serum) to the skin of their faces for eight weeks (56 days), twice daily, once in the morning and once in the evening. At day 28 (the four-week mark) and day 56 (the eight-week mark), we analyzed the treated areas for dermal density, skin elasticity; the length and area of crow’s feet; transepidermal water loss; facial and skin tone evenness; brightness; moisture retention/hydration; the size, depth, and number of wrinkles; roughness; skin hydration; and barrier function. We also evaluated the subjects’ perception and tolerance of the cream. The test regimen was well-tolerated by the study participants for various subjective parameters, including sensory attributes and improvement of overall skin conditions. The anti-aging regimen did not affect the skin barrier function and maintained baseline hydration. The test treatment provided statistically significant improvements in skin roughness and the depth of fine lines and wrinkles for fine wrinkles after 28 days of treatment. Furthermore, significant improvements were measured in skin elasticity for the firmness, maximal amplitude, and extensibility parameters after 56 days of treatment. The anti-aging regimen had a significant effect on skin elasticity. Patient perception of the apigenin containing regimen was excellent. Our findings support the evidence that apigenin can improve several markers of aging. Apigenin use in skin care products may contribute to objectively improved parameters of skin health and subjective appearance of photo-aged skin.

https://www.sciforschenonline.org/journals/clinical-cosmetic-dermatology/article-data/JCCD-2-128/JCCD-2-128.pdf

Best taken internally

Apigenin has been demonstrated to have VERY POWERFUL anti anxiety, anti depressive, anti Alzheimer’s and anti-excitotoxic neuroprotective capabilities

What is EXCITOTOXICITY?

“Excitotoxicity is the pathological process by which nerve cells are damaged or killed by excessive stimulation by neurotransmitters such as glutamate and similar substances. This occurs when receptors for the excitatory neurotransmitter glutamate (glutamate receptors) such as the NMDA receptor and AMPA receptor are overactivated by glutamatergic storm. Excitotoxins like NMDA and kainic acid which bind to these receptors, as well as pathologically high levels of glutamate, can cause excitotoxicity by allowing high levels of calcium ions (Ca2+) to enter the cell.[1][2] Ca2+ influx into cells activates a number of enzymes, including phospholipases, endonucleases, and proteases such as calpain. These enzymes go on to damage cell structures such as components of the cytoskeleton, membrane, and DNA.

Excitotoxicity may be involved in spinal cord injury, stroke, traumatic brain injury, hearing loss (through noise overexposure or ototoxicity), and in neurodegenerative diseases of the central nervous system (CNS) such as multiple sclerosis, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), Parkinson’s disease, alcoholism or alcohol withdrawal and especially over-rapid benzodiazepine withdrawal, and also Huntington’s disease.[3][4] Other common conditions that cause excessive glutamate concentrations around neurons are hypoglycemia.”

Apigenin modulates GABAergic and glutamatergic transmission in cultured cortical neurons

“Using the patch-clamp technique, we studied the modulation of ionotropic γ-aminobutyric acid (GABA) and glutamate neurotransmission by apigenin, a flavonoid with sedative and antidepressant activity. Apigenin reversibly reduced GABA-evoked currents mediated by α₁β₂γ₂ receptors expressed in HEK293 cells. Amplitude and frequency of spontaneous postsynaptic inhibitory currents (sIPSCs) mediated by GABA_A receptors were also decreased by apigenin in cultured cortical neurons. The flavonoid was almost inactive on α-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA) mediated currents while it reduced N-methyl-d-aspartate (NMDA) receptor mediated responses with a half maximal inhibiting concentration (IC₅₀) of 10 μM. The flavonoid inhibited also peak amplitude and frequency of spontaneous postsynaptic excitatory currents(sEPSCs). Finally, apigenin is neuroprotective against glutamate-induced neurotoxicity in cerebellar and cortical neurons in culture. Our data reveal the antagonistic effect of apigenin on GABA and NMDAchannels. While the inhibition on GABA receptorcannot explain the effects of the drug in vivo our data on NMDA channels reveal a new target of apigenin. A reduction of the network excitability could thus account for the sedative effects. Furthermore, our data suggest a potential neuroprotective activity of apigenin.”

Antidepressant-like behavioral and neurochemical effects of the citrus-associated chemical apigenin

“Apigenin is one type of bioflavonoid widely found in citrus fruits, which possesses a variety of pharmacological actions on the central nervous system. A previous study showed that acute intraperitoneal administration of apigenin had antidepressant-like effects in the forced swimming test (FST) in ddY mice. To better understand its pharmacological activity, we investigated the behavioral effects of chronic oral apigenin treatment in the FST in male ICR mice and male Wistar rats exposed to chronic mild stress (CMS). The effects of apigenin on central monoaminergic neurotransmitter systems, the hypothalamic–pituitary–adrenal (HPA) axis and platelet adenylyl cyclase activity were simultaneously examined in the CMS rats. Apigenin reduced immobility time in the mouse FST and reversed CMS-induced decrease in sucrose intake of rats. Apigenin also attenuated CMS-induced alterations in serotonin (5-HT), its metabolite 5-hydroxyindoleacetic acid (5-HIAA), dopamine (DA) levels and 5-HIAA/5-HT ratio in distinct rat brain regions. Moreover, apigenin reversed CMS-induced elevation in serum corticosterone concentrations and reduction in platelet adenylyl cyclase activity in rats. These results suggest that the antidepressant-like actions of oral apigenin treatment could be related to a combination of multiple biochemical effects, and might help to elucidate its mechanisms of action that are involved in normalization of stress-induced changes in brain monoamine levels, the HPA axis, and the platelet adenylyl cyclase activity.”

The Flavonoid Apigenin Protects Brain Neurovascular Coupling against Amyloid-β_25-35-Induced Toxicity in Mice

“Apigenin, one of the most common flavonoids, has demonstrated anti-inflammatory, anticarcinogenic, and free radical-scavenging activities. Recent studies revealed its protective effects against amyloid-β (Aβ)-induced neurotoxicity, but the mechanism was unclear. In the present study, we aimed to explore the anti-amnesic and protective effects of apigenin against Aβ25-35-induced toxicity and the underlying mechanisms in the cerebral cortex in mice. The learning and memory impairments, changes in morphology of major components of neurovascular unit, ultrastructural changes and oxidative stress of cerebral cortex, cerebrovascular dysfunction, and neuronal changes were detected after oral administration of apigenin continuously for 8 days. Our results demonstrate that oral administration of apigenin for Aβ25-35-induced amnesic mice conferred robust neurovascular coupling protection, involving improvement of the learning and memory capabilities, maintenance of neurovascular unit integrity, modulation of microvascular function, reduction of neurovascular oxidative damage, increase of regional cerebral blood flow, improvement of cholinergic system involving the inhibition of AChE activity and elevation of ACh level, and modification of BNDF, TrkB, and phospho-CREB levels.”

In the present study, apigenin inhibited the glutamate-induced [Ca2+]i increase by inhibiting AMPA-, NMDA-, and depolarization-induced Ca2+ influx. Apigenin also inhibited the metabotropic glutamate receptor-induced [Ca2+]i increase and Ca2+-induced Ca2+ release from intracellular stores. These data suggest a possibility that apigenin inhibits synaptic transmission. Reducing [Mg2+]o bathing cultured CNS neurons elicits [Ca2+]i spikes that depends upon glutaminergic synaptic transmission (Rose et al, 1990; Shen et al, 1996; Abel et al, 2000). In this study, apigenin inhibited the synaptically mediated low [Mg2+]o-induced [Ca2+]i spikes. These data suggest that apigenin inhibits glutamatergic synaptic transmission in cultured rat hippocampal neurons by inhibiting AMPA-, NMDA-, and depolarization-induced Ca2+ influx as well as metabotropic glutamate receptor-induced release of Ca2+ from IP3-sensitive intracellular stores and Ca2+-induced Ca2+ release from ryanodine-sensitive stores. However, it has not been studied in the present study whether apigenin affects the release of glutamate in the presynaptic sites, although apigenin inhibited the high K+-induced [Ca2+]i increase in the soma.

Apigenin has neuroprotective effects against oxidative stress-induced cell death in SH-SY5Y cells (Wang et al, 2001), or glutamate-induced neurotoxicity in cultured cortical neurons (Losi et al, 2004). Our results showed that apigenin inhibits glutamate-induced calcium signaling. These results suggest a possibility that inhibitory effects of apigenin on glutamate-induced calcium signaling can partly be due to the neuroprotection against neuronal cell death, demonstrating a possibility that apigenin might be used as a neuroprotective agent against glutamate-induced neurotoxicity, partly through inhibition of calcium signaling.

Protection of apigenin against excitotoxicity by anti-oxidative effects.

Apigenin (5,7,4′-trihydroxyflavone) is a principal ingredient of Cirsium japonicum. These experiments were performed to determine whether apigenin has neuroprotective effects against kainic acid (KA)-induced excitotoxicity in vitro and in vivo. Intraperitoneal (i.p.) administration of apigenin (25, 50 mg/kg) decreased the seizure scores induced by KA injection (40 mg/kg, i.p.) in mice. In addition, the convulsion onset time was significantly delayed by apigenin administration. Moreover, we found that apigenin blocked KA-induced seizure-form electroencephalogram (EEG) discharge activity in the brain cortex. In hippocampal cells, apigenin inhibited KA-induced excitotoxicity in a dose-dependent manner as measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. To study the possible mechanisms underlying the in vitro neuroprotective effects of apigenin against KA-induced cytotoxicity, we also examined the effect of apigenin on intracellular reactive oxygen species (ROS) elevations in cultured hippocampal neurons and found that apigenin treatment dose-dependently inhibited intracellular ROS elevation. The remarkable reduction of glutathione (GSH) levels induced by KA in hippocampal tissues was reversed by apigenin in a dose-dependent manner. In addition, similar results were obtained after pretreatment with free radical scavengers such as trolox and dimethylthiourea (DMTU). Finally, after confirming the protective effect of apigenin in hippocampal CA3 region, we found apigenin is an active compound in KA-induced neuroprotection. These results collectively indicate that apigenin alleviates KA-induced excitotoxicity by quenching ROS as well as inhibiting GSH depletion in hippocampal neurons.

Neuroprotective effects of apigenin against inflammation, neuronal excitability and apoptosis in an induced pluripotent stem cell model of Alzheimer’s disease.

“Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative diseases, yet current therapeutic treatments are inadequate due to a complex disease pathogenesis. The plant polyphenol apigenin has been shown to have anti-inflammatory and neuroprotective properties in a number of cell and animal models; however a comprehensive assessment has not been performed in a human model of AD. Here we have used a human induced pluripotent stem cell (iPSC) model of familial and sporadic AD, in addition to healthy controls, to assess the neuroprotective activity of apigenin. The iPSC-derived AD neurons demonstrated a hyper-excitable calcium signalling phenotype, elevated levels of nitrite, increased cytotoxicity and apoptosis, reduced neurite length and increased susceptibility to inflammatory stress challenge from activated murine microglia, in comparison to control neurons. We identified that apigenin has potent anti-inflammatory properties with the ability to protect neurites and cell viability by promoting a global down-regulation of cytokine and nitric oxide (NO) release in inflammatory cells. In addition, we show that apigenin is able to protect iPSC-derived AD neurons via multiple means by reducing the frequency of spontaneous Ca(2+) signals and significantly reducing caspase-3/7 mediated apoptosis. These data demonstrate the broad neuroprotective action of apigenin against AD pathogenesis in a human disease model.”

Apigenin: A Promising Molecule for Cancer Prevention

“Apigenin, a naturally occurring plant flavone, abundantly present in common fruits and vegetables is recognized as a bioactive flavonoid shown to possess anti-inflammatory, antioxidant and anticancer properties. Epidemiologic studies suggest that a diet rich in flavones is related to a decreased risk of certain cancers, particularly cancers of the breast, digestive tract, skin, prostate and certain hematological malignancies. It has been suggested that apigenin may be protective in other diseases that are affected by oxidative process such as cardiovascular and neurological disorders, although more research needs to be conducted in this regard. Human clinical trials examining the effect of supplementation of apigenin on disease prevention have not been conducted although there is considerable potential for apigenin to be developed as a cancer chemopreventive agent.”

APIGENIN STIMULATES HAIR GROWTH through downregulation of the TGF-β1 gen

“Androgen-inducible transforming growth factor β (TGF-β1) derived from dermal papilla cells (DPCs) is a catagen inducer that mediates hair growth suppression in androgenetic alopecia (AGA). In this study, a cell-based assay system was developed to monitor TGF-β1 promoter activity and then used to evaluate the effects of activated TGF-β1 promoter in human epidermal keratinocytes (HaCaT). To accomplish this, a pMetLuc-TGF-β1 promoter plasmid that expresses the luciferase reporter gene in response to TGF-β1 promoter activity was constructed. Treatment of HaCaT with dihydrotestosterone, which is known to be a primary factor of AGA, resulted in a concentration-dependent increase in TGF-β1 promoter activity. However, treatment of HaCaT with the TGF-β1 inhibitor, curcumin, resulted in a concentration-dependant decrease in TGF-β1 expression. Subsequent use of this assay system to screen TGF-β1 revealed that HaCaT that were treated with apigenin showed decreased levels of TGF-β1 expression. In addition, treatment with apigenin also significantly increased the proliferation of both SV40T-DPCs (human DPCs) and HaCaT cells. Furthermore, apigenin stimulated the elongation of hair follicles in a rat vibrissa hair follicle organ culture. Taken together, these findings suggest that apigenin, which is known to have antioxidant, anti-inflammatory, and anti-tumor properties, stimulates hair growth through downregulation of the TGF-β1 gene.”

* LONG HALF LIFE; builds up over time. “Blood kinetics showed a high elimination half-time (91.8 hr), a distribution volume of 259 mL, and a plasmatic clearance of 1.95 mL/hr. All of the parameters calculated from these experiments suggested a slow metabolism of apigenin, with a slow absorption and a slow elimination phase. Thus, a possible accumulation of this flavonoid in the body can be hypothesized.”https://www.sciencedirect.com/science/article/pii/S0955286310000379

200 MORE SCIENTIFIC STUDIES ON APIGENIN

8 reviews for APIGENIN 200:1

Rated 5 out of 5
CC – August 20, 2018
Though I have only been taking this for a little while compared to taking the spice and peel for a much longer time. I can tell that my joints feel like they have less inflammation. A few days ago I was in a lot of pain and Gavin told me to take a megadose of spice which I did and then I added a scoop of the apeginin and the pain subsided even more. I was very grateful for the lessened pain. I look forward to seeing how my joints continue to feel.
Rated 5 out of 5
Stephen – December 31, 2018
I initially ordered this with Spice/Peel about three months ago to train for a professional event, after asking Gavin for advice on what to take.
I’ve been training twice a day since then and remarkably my blood tests showed my free testosterone has improved! I’ve struggled with my free testosterone levels for several years now and I’m really amazed this worked.
I’ve just ordered the 10 spice combo and look forward to taking my training to the next level!
Rated 5 out of 5
Luz Carter – June 29, 2019
My latest purchase was Apigenin. I bought this one due to the effect of healing in the liver. I have what’s known as esophageal varices. They were discovered when I was in my mid twenties. I’m not a heavy drinker by any means. From what we can tell it’s due to when I had my spleen removed and apparently an injured portal vein as a premie. I had my gall bladder out shortly after my daughter was born 13 years ago and they nicked one of the varices during that surgery. To this day I still have a blood clot near that area. I’m taking Apigenin as another means to heal my insides. I can tell a difference already. I don’t ache as much in that area anymore and I’m continuing to lose belly fat with dry fasting and the blends. Definitely keeping this one in my arsenal. Gavin, you are the “Master of Herbs” and I’m so glad I placed an order. I am a life long believer in your product and I tell people every day how much these blends have improved my health. Keep doing what you’re doing because you’re changing the lives of MANY!
Rated 5 out of 5
Rich Ryan – August 21, 2019
“Wanted to share that I’ve experienced a significant decrease in my heart disease symptoms over the last year since I doubled my Spice/Peel intake. I can tell the main blockage on my Widow Maker artery on the back of my heart, that I’ve been carrying for over 15 years, has shrunk significantly. The proof is that when I have a bad day and eat all kinds of crap that I shouldn’t eat, I experience almost no symptoms from it. A year ago I would’ve almost died from eating all that garbage. Now, almost nothing.
Also, my depression is pretty much gone since starting Apigenin, Luteolin, and supplementing with Mag, Zinc and Lithium. 1/4 tsp API, 1/2 tsp Lut, 4 caps Mag and Zinc, 10 drops Lithium. Twice a day for all.
My Spice/Peel intake is 2 tsp 20:1, 1/2 tsp 200:1. I alternate between 20:1 and 200:1. Usually do one of them 20:1 and the other 200:1, and switch it up every month or two. Take one in the morning, the other in the evening.
So Gavin has hit on the cure for arterial blockages as well. Amazing stuff!”
Rated 5 out of 5
michael mannino – April 8, 2020
Apegenin has been a game changer. I have been taking Apegenin for over a year now. I was prescribed Ritalin since the age of 13, I always skipped my doses and denied any of the anti depressants the doctors always offered me. After years of battling with depression from the drugs, I finally rid my body of all these artificial, dangerous, and unhealthy chemicals from my lifestyle. That was a long time ago, and since then I have been always searching for uplifting, health enhancing, anti-aging elements to pair with my diet. I searched for years for ancient herbs, finally I found Gavin through my friends group and thank god for that. I always praise his products because they have given me the chance to challenge myself and have major benefits at the same time. These products may seem like a hefty investment, but what does your health and your life at the very core mean to you? If filling your body with chocolate and soda is your answer, then this probably isn’t for you(and maybe SHOULD BE). If you want to start a new healthy lifestyle, or continue fulfilling your goals and add a powerful, life-changing element into the mix to join you, then what the F&^% are you waiting for? I’m about to get another batch, using these blends are the favorite part of my day and I always look forward to continuing life and smashing the impossible with them by my side. Cheers Gavin, and thank you!!!
Rated 5 out of 5
Paul Benson (verified owner) – September 29, 2020
Alright, I’ve got to talk about apigenin for a moment here. I told Gavin some of my issues, and he got back to me (within minutes, the guy’s a beast) with his recommendations. I’ve tried and use a fair amount of the blends, but I hadn’t used apigenin yet. So I gave it try.
I’m not one to write a review just after a few days of taking a supplement or medicine. I’ve been around long enough and tried enough supplements and medicines that I know I need to use it for at least a month, but preferably, several months before I can give an honest review. And the long and short of it is, after around four months of taking apigenin, I recommend it.
Now, it took me a bit to figure out the right timing to take apigenin, so I’d encourage you to give it a few days and if you notice anything negative, try what I did first and then see where you are from there. What I learned is that if I took it first thing in the morning and on its own, it gave me a powerful boost for the day, lowered the heart problems I’ve dealt with for years, and gave me a bigger drive (both libido and life, though I think both are highly related).
I’ll go into a bit more detail here. Because it’s powerful and can increase testosterone, I’ll share a bit of detail that may be too much for some, but something I think every guy should know, and which I’ll get to in a minute. But first, the effects on my heart. I’ve had a condition known as Prinzmetal Angina for the past 18 years (this Oct is the 18th anniversary). Spice was a game-changer, and I truly believe saved my life, but I also wanted to add a bit more because there was a ton of damage done over the years. Spice took the constant pain and the ick feeling away–what Apigenin has done has helped lower the amount of spasms I’ve been experiencing (Prinzmetal, or variant, angina, is where the coronary arteries spasm). What this translates to is more energy and stamina, and less pain and exhaustion overall. When a spasm comes, it can leave me wiped out, so not having as many has been huge.
Next, I literally started getting more tiny hairs growing on my head. (Makes me think adding in the Hair Tonic would be a good idea!) I’ve said for years that my one vanity is having hair, so when it started thinning that sucked. This has literally been helping restore the hair.
Now for the “guy” part. If it’s too much info, sorry, but I think it’s important, especially in our time when there are so many estrogen boosters in so many products from medicine to food to even detergents. After about a month of consistent use, I noticed that the boys started feeling heavier. Not much mind you, but a little bit. I wasn’t sure if I was just imagining things, and so I’ve paid close attention. And over the months, they grew. In fact, just from the feel alone, now I’d say they weigh 1.5-2 times more than what they did before. This is no exaggeration. I’m a lot fuller than I’ve ever been down there and now in the bedroom, there’s been a lot less frustration on both mine and my wife’s part. And even though I’ve been getting older, I can perform better now and more often than I could for probably the last six to seven years.
All in all, I love this product, and I HIGHLY recommend it!
Rated 5 out of 5
Alecxander Castro – October 14, 2020
I first heard from Interstellar blends from Shaun Lee on Instagram. I hesitated cuz of the price but after a few months I dove in and got every single product from Gavin to see which one was best for my lifestyle.
I work in a hedgefund so I need to have my brain on point all the time and I found that my favorite herbs were: Apigenin, Shilajit, Victorious, Peel, Spice, ALZ, Luteolin, Hypnotic to sleep, Super Tonic Hair, and Pine Pollen. I take them pure with hot water.
I lead a pretty active and healthy lifestyle and I found that combining these blends with my morning green shake of veggies and fruits, my cognitive functions and my brain in general works so much better. It even helps me to meditate more deeply and productively. They will be in my arsenal of tools to boost my brain. The more you use Apigenin, the more brain cells you form in your brain cuz of neuro genesis. How cool is that! If I understand it correctly, you get smarter by every month using it while leading a healthy lifestyle!
Rated 5 out of 5
Milan (verified owner) – July 25, 2021
This is a great all round product, I have been using the blends for almost a year now, beginning with the starter pack and then using almost all the different products. This has to be my new favourite, it you’re looking for that extra edge, mental clarity, increased muscle strength and less fatigue!
Thanks gavin for the amazing, life changing blends!

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APIGENIN 200:1

Apigenin and related compounds stimulate adult neurogenesis

New approach in treatment of brain injury: Neurotrophic effects of Apigenin

Apigenin modulates GABAergic and glutamatergic transmission in cultured cortical neurons

Antidepressant-like behavioral and neurochemical effects of the citrus-associated chemical apigenin

The Flavonoid Apigenin Protects Brain Neurovascular Coupling against Amyloid-β25-35-Induced Toxicity in Mice

Protection of apigenin against excitotoxicity by anti-oxidative effects.

8 reviews for APIGENIN 200:1

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The Flavonoid Apigenin Protects Brain Neurovascular Coupling against Amyloid-β_25-35-Induced Toxicity in Mice