COROSOLIC ACID - Glucose Control, Insulin Sensitivity, Cortisol Lowering

Lokzo

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Mechanisms of Action
Corosolic acid is suggested to induce GLUT4 translocation [9,10]. Translocation of more GLUT4 glucose transporters to the cell surface means increased insulin action [11]. Disrupted GLUT4 gene has been shown to cause insulin resistance in skeletal muscles as well as diabetes [12]. Corosolic acid also works as “insulin sensitizer” by inhibiting enzymatic activities of several diabetes-related non-receptor protein tyrosine phosphatases (such as PTP1B) which indirectly enhances insulin receptor B phosphorylation [9]. Inhibition of protein tyrosine phosphatase 1B is an attractive target for treatment of diabetes and obesity [13,14]. Corosolic acid also promotes glycolysis [5] and suppresses gluconeogenesis (via increased production of fructose-2,6-bisphosphate) [15].


Cortisol Regulation
Corosolic acid is a potent and selective inhibitor of the enzyme (11-beta hydroxysteroid dehydrogenase type 1) that converts inactive cortisone to active cortisol [18]. Therefore, corosolic acid may prevent excessive cortisol production.




  1. Hamamoto S, et al. “Glucosol effect on blood glucose in rats. Yakuri to Chiryo”. 27.6 (1999): 1075-1077.
  2. Judy, William V., et al. “Antidiabetic activity of a standardized extract (Glucosol™) from Lagerstroemia speciosa leaves in Type II diabetics: A dose-dependence study.” Journal of Ethnopharmacology 87.1 (2003): 115-117.
  3. Miura, Toshihiro, et al. “Antidiabetic effects of corosolic acid in KK-Ay diabetic mice.” Biological and Pharmaceutical Bulletin 29.3 (2006): 585-587.
  4. Tsuchibe, S., et al. “An inhibitory effect on the increase in the postprandial glucose by banaba extract capsule enriched corosolic acid.” Journal for the Integrated Study of Dietary Habits 17 (2006): 255-259.
  5. Stohs, Sidney J., Howard Miller, and Gilbert R. Kaats. “A review of the efficacy and safety of banaba (Lagerstroemia speciosa L.) and corosolic acid.” Phytotherapy Research 26.3 (2012): 317-324.
  6. Fukushima, M., et al. “Effect of corosolic acid on postchallenge plasma glucose levels.” Diabetes research and clinical practice 73.2 (2006): 174-177.
  7. Jiao, Sheng, et al. “Decreased activity of acyl-CoA: cholesterol acyltransferase by insulin in human intestinal cell line Caco-2.” Diabetes 38.5 (1989): 604-609.
  8. Takagi, Satoshi, et al. “Effect of corosolic acid on dietary hypercholesterolemia and hepatic steatosis in KK-Ay diabetic mice.” Biomedical Research 31.4 (2010): 213-218.
  9. Miura, Toshihiro, et al. “Corosolic acid induces GLUT4 translocation in genetically type 2 diabetic mice.” Biological and pharmaceutical bulletin 27.7 (2004): 1103-1105.
  10. Shi, Lei, et al. “Corosolic acid stimulates glucose uptake via enhancing insulin receptor phosphorylation.” European journal of pharmacology 584.1 (2008): 21-29.
  11. Holloszy, John O. “Exercise-induced increase in muscle insulin sensitivity.”Journal of Applied Physiology 99.1 (2005): 338-343.
  12. Stenbit, Antine E., et al. “GLUT4 heterozygous knockout mice develop muscle insulin resistance and diabetes.” Nature medicine 3.10 (1997): 1096-1101.
  13. Pei, Zhonghua, et al. “Inhibition of protein tyrosine phosphatase 1B as a potential treatment of diabetes and obesity.” Current pharmaceutical design 10.28 (2004): 3481-3504.
  14. Zhang, Zhong-Yin, and Seung-Yub Lee. “PTP1B inhibitors as potential therapeutics in the treatment of type 2 diabetes and obesity.” Expert opinion on investigational drugs 12.2 (2003): 223-233.
  15. Yamada, Kotaro, et al. “Effect of corosolic acid on gluconeogenesis in rat liver.” Diabetes research and clinical practice 80.1 (2008): 48-55.
  16. Sivakumar, Ganapathy, et al. “Plant‐based corosolic acid: Future anti‐diabetic drug?.” Biotechnology journal 4.12 (2009): 1704-1711.
  17. Jang, Dae Sik, et al. “A new pancreatic lipase inhibitor isolated from the roots of Actinidia arguta.” Archives of pharmacal research 31.5 (2008): 666-670.
  18. Deanna J. Fall, BA and Sirid-Aimée Kellermann. “Addressing Adrenal Imbalance: The Future of Adrenal health.” NeuroScience, Inc.
 
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Lokzo

Lokzo

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Thank you, this is very helpful and interesting.

No worries! I'm excited to trial it around dinner time, to see how potent the cortisol lowering effects are, and also to see if I can get my fasting sugar below 4.6.
Also, want to be as insulin sensitive as I can, since my fasting insulin is already 5!!! (I'm 22).
 

managing

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No worries! I'm excited to trial it around dinner time, to see how potent the cortisol lowering effects are, and also to see if I can get my fasting sugar below 4.6.
Also, want to be as insulin sensitive as I can, since my fasting insulin is already 5!!! (I'm 22).
How are you obtaining it? Seems to be available from "banaba extract" ? What are you using?
 
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Lokzo

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It has arrived in the mail. Given one to my father (Type 2 diabetic), it is the afternoon now, we will see if it is able to reduce his stress (And everything else associated with reducing cortisol).

Will keep you all updated.

I *Might* try it tonight after dinner myself.
 
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Lokzo

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You can use this as pre-workout with sugar.

That was exactly how I was planning on using it. Or with my MASSIVE carb meals for better glucose uptake. Hoping it will help me stay lean during bulks.

I am trying to uncover it's half life, but that seems tricky. Not sure if any research has been conducted on this.
 

Terma

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Yeah, thanks, this seems legit. Studies from 15 years ago no less. Makes me wonder what else this forum is missing.
Antidiabetic activity of a standardized extract (Glucosol™) from Lagerstroemia speciosa leaves in Type II diabetics: A dose-dependence study - ScienceDirect (hepatocytes here)
While a cAMP-dependent protein kinase (PKA) inhibitor inhibited hepatic gluconeogenesis, the drug did not intensify the inhibitory effect of CRA on hepatic gluconeogenesis in isolated hepatocytes. These results indicate that CRA inhibits gluconeogenesis by increasing the production of F-2,6-BP by lowering the cAMP level and inhibiting PKA activity in isolated hepatocytes.
 
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Lokzo

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Yeah, thanks, this seems legit. Studies from 15 years ago no less. Makes me wonder what else this forum is missing.
Antidiabetic activity of a standardized extract (Glucosol™) from Lagerstroemia speciosa leaves in Type II diabetics: A dose-dependence study - ScienceDirect (hepatocytes here)

Are you wanting more human studies?

I dosed about an hour ago, and have noticed that "catching breath" feeling, reduced manic after dinner energy, and much calmer. Looking forward to seeing how I sleep tonight.
 

Terma

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Not really, the ones you linked are not bad (relatively). I mean you could get way more discriminatory at this point (FDA trials). Was just interested in the mechanism, and cAMP inhibition is believable. So n=1 sounds good.
 

managing

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Are you wanting more human studies?

I dosed about an hour ago, and have noticed that "catching breath" feeling, reduced manic after dinner energy, and much calmer. Looking forward to seeing how I sleep tonight.
Very interested in the ongoing report . . .
 
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Lokzo

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Very interested in the ongoing report . . .

Slept a mega 9.5 hours. I do have a cold at the moment, but do feel very rested.
I'm not going to measure my fasting sugar under these conditions (Haven't been training and my diet has been different due to this cold)

But from a GI point of view, no major irritations.
Appetite seems more suppressed than usual.

I think it may be a winner in my books.

Will continue to test it out.
 

managing

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Slept a mega 9.5 hours. I do have a cold at the moment, but do feel very rested.
I'm not going to measure my fasting sugar under these conditions (Haven't been training and my diet has been different due to this cold)

But from a GI point of view, no major irritations.
Appetite seems more suppressed than usual.

I think it may be a winner in my books.

Will continue to test it out.
:+1
 
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Lokzo

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Wow. Okay, took my sugars this afternoon, and was surprised by how low it was!! I've never seen it reach this... 4.3

Keep in mind that was just from dosing before bed.

I have just dosed again straight after the reading to see if it drops it even lower... Bracing myself for Hypoglycaemic symptoms!!!
#SugarOnStandby
 
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Lokzo

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Wow. Okay, took my sugars this afternoon, and was surprised by how low it was!! I've never seen it reach this... 4.3

Keep in mind that was just from dosing before bed.

I have just dosed again straight after the reading to see if it drops it even lower... Bracing myself for Hypoglycaemic symptoms!!!
#SugarOnStandby

So 90 mins after dosing, it dropped to 4.1.

Again, that is the lowest I've seen my sugar levels in the afternoon for a while. Not bad.
 
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Lokzo

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I might just add that I've found even more research and useful information:
Antidiabetic activity

As an antidiabetic agent, L. speciosa has several modes of action. It has a hypoglycemic effect and acts as a glucose transport enhancer. It also exhibits insulin-mimetic (peptide analogs) activity, stimulates insulin receptors, activates GLUT4, and is an alpha-amylase and alpha-glucosidase inhibitor.[43],[44],[45],[46],[47],[48],[49],[50],[51],[52],[53]

The hypoglycemic effects

The effect of hypoglycemic from L. speciosa has been studied using hereditary diabetic mice (Type II, KK-AY/Ta JcI). The administration of a hot water extract of L. speciosa can suppress the elevation of blood plasma glucose level in noninsulin-dependent diabetic mice fed a cellulose diet as a control. It was also observed that water intake increased gradually in the group fed either cellulose diet or a partial fraction of hot water extract. However, the mice fed either a hot water extract or partial fraction of L. speciosa had a lower intake of water. Other parameters, such as serum insulin levels, urinary glucose excretion, and total plasma cholesterol also decreased in mice fed with water extract of L. speciosa. The hot water extract reduced the levels of plasma glucose and insulin and improved diabetic symptoms in noninsulin-dependent diabetic mice. In addition, the plant extract also reduced total plasma cholesterol levels.[43] Another study also revealed that L. speciosa possesses beneficial antihyperglycemic activity by controlling glucose levels in alloxan-induced diabetic mice.[44]

Glucose transport enhancers

The antidiabetic properties of L. speciosa have been widely investigated from in vitro to human studies. Kakuda et al., (1996) has identified the reduction of level of plasma glucose and insulin in hereditary type 2 diabetic mice. In addition, the plasma cholesterol levels in treated mice were significantly reduced, indicating that L. speciosa leaf extracts restrained or delayed cholesterol absorption in the intestine.[43] In another study, it was shown in 3T3-L1 adipocytes, the water extract of L. speciosa stimulated glucose uptake. In addition, the benefit of this plant is that unlike insulin, L. speciosa has the ability to reduce the side effects of weight gain in the treatment of type 2 diabetes because the plant extract does not regulate lipid biosynthesis in adipocytes, and the plant can inhibit the differentiation of adipocyte. Another study has revealed several active components such as ellagitannins, lagerstroemin, flosin B, and reginin that contribute to its antidiabetic activity. These components have been isolated from the leaf of the plant and have been shown to increase glucose uptake and lower glucose levels in rats. Lagerstroemin produced dose-dependent glucose transport activity from concentrations of 0.02-0.30 mM. This result suggests activity similar to insulin and was reported to decrease blood glucose levels in patients with diabetes.[18]

Insulin-mimetic (peptide analogs) activity

Small components identified in Lagerstroemia as alpha- and beta-pentagalloylglucose (PGG) (α- and β-PGG) showed insulin-mimetic activities. α-PGG is more potent than β-PGG. α-PGG also stimulates translocation of GLUT4,[48] inhibits differentiation of preadipocytes, and targets insulin receptors.

Stimulation of insulin receptors

Stimulation of insulin receptors can cause phosphorylation of several proteins on tyrosine residues. Hattori et al.[49] found that a L. speciosacompound called lagerstroemin induces tyrosine-phosphorylation of IR (insulin receptor). This study suggested that lagerstroemin can act as an antidiabetic drug, such as metformin, by activating insulin receptors.

GLUT4 activation

GLUT4 is a protein in muscle and adipose cells. This protein transports glucose across the plasma membrane, allowing cells to gain energy and maintain healthy blood sugar levels. When the transporters are in the plasma membrane, glucose enters into the cytoplasm and is converted to glucose-6-phosphate (G6P) by hexokinase HK, thus promoting the glycogen synthesis. Physical exercise is widely known to maintain healthy glucose metabolism because it enhances GLUT 4 levels in muscle. Miura et al.(2004) reported that corosolic acid can cause GLUT4 translocation into the plasma membrane and induce uptake of glucose into the cells, lowering glucose levels in the blood.[50] The mechanism of action of corosolic acid is that it stimulates glucose uptake by enhancing insulin receptor phosphorylation, similar to the function of pioglitazone (Actos) and rosiglitazone (Avandia).[51]

Fructose-2,6-bisphosphate (F-2,6-BP) plays a role in liver gluconeogenesis and glycolysis, which effects glucose production. Corosolic acid acts as an inhibitor of gluconeogenesis by increasing the level of F-2,6-BP and inhibiting PKA activity in isolated hepatocytes. The activity on hepatic glucose metabolism may underlie the antidiabetic activity of corosolic acid.[52] Rosiglitazone (Avandia), pioglitazone (Actos), and metformin (Glucophage) can decrease glucose production, whereas L. speciosa does not. Thus, L. speciosa showed better efficacy compared to those drugs.

Alpha-amylase and alpha-glucosidase inhibitors

In one study, L. speciosa tea caused a 38% reduction of alpha-amylase activity. Another study suggested methanol and water extracts of L. speciosa reduces alpha-amylase and alpha-glucosidase activity. Both enzymes are involved in the digestion of carbohydrates, which increases glucose levels. Inhibiting these enzymes causes a delay of carbohydrate absorption, therefore decreasing blood sugar levels.[20],[53]

(Revisiting bungur (Lagerstroemia speciosa) from Indonesia as an antidiabetic agent, its mode of action, and phylogenetic position Nurcahyanti AD, Arieselia Z, Kurniawan SV, Sofyan F, Wink M - Phcog Rev)
 

managing

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This is very interesting. How are you timing the dosage? In conjunction with ameal?
 

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