Yangonin protects against non-alcoholic fatty liver disease

[TheKavaSociety]

https://www.sciencedirect.com/science/article/pii/S0944711318302873

Abstract
Backgroud
Non-alcoholic fatty liver disease (NAFLD) is currently evolving as the most common liver disease worldwide. Dyslipidemia, pathoglycemia and insulin resistance are the major risk factors for the development of NAFLD. To date, no effective drug therapies for this condition have been approved.

Purpose
The present study was to investigate the protective effects of yangonin, a kavalactone isolated from Kava, against NAFLD and further elucidate the mechanisms in vivo and in vitro.

Study design
A high-fat diet (HFD) induced mouse NAFLD model was used with or without yangonin treatment.

Methods
The body weight, relative liver weight and serum biochemical indicators were measured. H&E and Oil Red O staining were used to identify the amelioration of the liver histopathological changes. Serum and hepatic triglyceride, free fatty acids and total cholesterol were analyzed. siRNA, quantitative real-time PCR and Western blot assay were used to clarify the mechanisms underlying yangonin protection.

Results
Yangonin had obvious protective effects against NAFLD via farnesoid X receptor (FXR) activation. Through FXR activation, yangonin attenuated lipid accumulation in the liver via inhibition of hepatic lipogenesis-related protein including sterol regulatory element-binding protein 1c (SREBP-1c), fatty acid synthetase (FAS), acetyl-CoA carboxylase 1 (ACC1) and stearoyl-CoA desaturase 1 (SCD1). Besides, yangonin promoted lipid metabolism through an induction in genes required for lipoprotein lipolysis and fatty acid β-oxidation. Furthermore, yangonin modulated blood glucose homeostasis through regulation of gluconeogenesis-related gene phosphoenol pyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase), and glycogen synthesis-related gene glycogen synthase kinase 3β (GSK3β) and pyruvate dehydrogenase (PDase). Also, yangonin increased insulin sensitivity through upregulating phosphorylation of insulin responsive substrate 1, 2 (IRS-1 and IRS-2). Then, in vivo and in vitro evidence further demonstrated the involvement of FXR activation in yangonin hepatoprotection.

Conclusions
Yangonin protects against NAFLD due to its activation of FXR signalling to inhibit hepatic lipogenesis and gluconeogenesis, and to promote lipid metabolism and glycogen synthesis, as well as insulin sensitivity.

 

[tarragon]

https://www.sciencedirect.com/science/article/pii/S0944711318302873

Abstract
Backgroud
Non-alcoholic fatty liver disease (NAFLD) is currently evolving as the most common liver disease worldwide. Dyslipidemia, pathoglycemia and insulin resistance are the major risk factors for the development of NAFLD. To date, no effective drug therapies for this condition have been approved.

Purpose
The present study was to investigate the protective effects of yangonin, a kavalactone isolated from Kava, against NAFLD and further elucidate the mechanisms in vivo and in vitro.

Study design
A high-fat diet (HFD) induced mouse NAFLD model was used with or without yangonin treatment.

Methods
The body weight, relative liver weight and serum biochemical indicators were measured. H&E and Oil Red O staining were used to identify the amelioration of the liver histopathological changes. Serum and hepatic triglyceride, free fatty acids and total cholesterol were analyzed. siRNA, quantitative real-time PCR and Western blot assay were used to clarify the mechanisms underlying yangonin protection.

Results
Yangonin had obvious protective effects against NAFLD via farnesoid X receptor (FXR) activation. Through FXR activation, yangonin attenuated lipid accumulation in the liver via inhibition of hepatic lipogenesis-related protein including sterol regulatory element-binding protein 1c (SREBP-1c), fatty acid synthetase (FAS), acetyl-CoA carboxylase 1 (ACC1) and stearoyl-CoA desaturase 1 (SCD1). Besides, yangonin promoted lipid metabolism through an induction in genes required for lipoprotein lipolysis and fatty acid β-oxidation. Furthermore, yangonin modulated blood glucose homeostasis through regulation of gluconeogenesis-related gene phosphoenol pyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase), and glycogen synthesis-related gene glycogen synthase kinase 3β (GSK3β) and pyruvate dehydrogenase (PDase). Also, yangonin increased insulin sensitivity through upregulating phosphorylation of insulin responsive substrate 1, 2 (IRS-1 and IRS-2). Then, in vivo and in vitro evidence further demonstrated the involvement of FXR activation in yangonin hepatoprotection.

Conclusions
Yangonin protects against NAFLD due to its activation of FXR signalling to inhibit hepatic lipogenesis and gluconeogenesis, and to promote lipid metabolism and glycogen synthesis, as well as insulin sensitivity.

That is good news Henry. Of course, we could all just not eat saturated fats, but I am glad kava helps. So many people I know are pre-diabetic. Alas they are also frequent social alcohol drinkers, so I don,t think they want to give that up or give up eating meat either. Kava promotes insulin sensitivity, so that means it helps to regulate blood sugar levels? Henry, have you any information about how kava affects the health of our gut biome? I would eagerly ingest any knowledge you may provide on this topic.

 

[Alia]

That is good news Henry. Of course, we could all just not eat saturated fats, but I am glad kava helps. So many people I know are pre-diabetic. Alas they are also frequent social alcohol drinkers, so I don,t think they want to give that up or give up eating meat either. Kava promotes insulin sensitivity, so that means it helps to regulate blood sugar levels? Henry, have you any information about how kava affects the health of our gut biome? I would eagerly ingest any knowledge you may provide on this topic.

I think there is such a paper regarding biome in kava in us and elsewhere. If you PM me I think I can get you a copy.

 

[Alia]

https://www.sciencedirect.com/science/article/pii/S0944711318302873

Abstract
Backgroud
Non-alcoholic fatty liver disease (NAFLD) is currently evolving as the most common liver disease worldwide. Dyslipidemia, pathoglycemia and insulin resistance are the major risk factors for the development of NAFLD. To date, no effective drug therapies for this condition have been approved.

Purpose
The present study was to investigate the protective effects of yangonin, a kavalactone isolated from Kava, against NAFLD and further elucidate the mechanisms in vivo and in vitro.

Study design
A high-fat diet (HFD) induced mouse NAFLD model was used with or without yangonin treatment.

Methods
The body weight, relative liver weight and serum biochemical indicators were measured. H&E and Oil Red O staining were used to identify the amelioration of the liver histopathological changes. Serum and hepatic triglyceride, free fatty acids and total cholesterol were analyzed. siRNA, quantitative real-time PCR and Western blot assay were used to clarify the mechanisms underlying yangonin protection.

Results
Yangonin had obvious protective effects against NAFLD via farnesoid X receptor (FXR) activation. Through FXR activation, yangonin attenuated lipid accumulation in the liver via inhibition of hepatic lipogenesis-related protein including sterol regulatory element-binding protein 1c (SREBP-1c), fatty acid synthetase (FAS), acetyl-CoA carboxylase 1 (ACC1) and stearoyl-CoA desaturase 1 (SCD1). Besides, yangonin promoted lipid metabolism through an induction in genes required for lipoprotein lipolysis and fatty acid β-oxidation. Furthermore, yangonin modulated blood glucose homeostasis through regulation of gluconeogenesis-related gene phosphoenol pyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase), and glycogen synthesis-related gene glycogen synthase kinase 3β (GSK3β) and pyruvate dehydrogenase (PDase). Also, yangonin increased insulin sensitivity through upregulating phosphorylation of insulin responsive substrate 1, 2 (IRS-1 and IRS-2). Then, in vivo and in vitro evidence further demonstrated the involvement of FXR activation in yangonin hepatoprotection.

Conclusions
Yangonin protects against NAFLD due to its activation of FXR signalling to inhibit hepatic lipogenesis and gluconeogenesis, and to promote lipid metabolism and glycogen synthesis, as well as insulin sensitivity.

Wonderful that you found this . Thank you for posting it. I will try and get a full copy soon.

 

[tarragon]

I think there is such a paper regarding biome in kava in us and elsewhere. If you PM me I think I can get you a copy.

Thank you!

 

[The Kap'n]

Thank you @Henry for this. So much still to be known, but man, doesn't it look bright when we get glimpses.

 

[Sean Wolf]

I have tried Kava today, and the past 2 days as well. It has provided wonderful pain relief, but something bizarre just happened. I am also an RN. I just had this sudden, scary episode of what felt like severe hypoglycemia 2 or so hours after taking Kava. I sweated and was losing consciousness and was extremely hungry. It is resolving after much apple juice. The thing is this: Kava may not cause low blood sugar, but LIVER DAMAGE can and will cause low blood sugar. It is because the liver stores sugar for our body to use later, when we need it. If liver injury prevents this (gluconeogenesis in the liver), you will experience low blood sugar. I am taking it as an ominous sign. I am so disheartened. For most people, this won't happen, I imagine, unless the liver stops working right. I happen to have a remote history of severe alcohol abuse and may not be working with much healthy liver tissue to begin with. I don't believe I should ever take Kava again.

 

[The Kap'n]

I have tried Kava today, and the past 2 days as well. It has provided wonderful pain relief, but something bizarre just happened. I am also an RN. I just had this sudden, scary episode of what felt like severe hypoglycemia 2 or so hours after taking Kava. I sweated and was losing consciousness and was extremely hungry. It is resolving after much apple juice. The thing is this: Kava may not cause low blood sugar, but LIVER DAMAGE can and will cause low blood sugar. It is because the liver stores sugar for our body to use later, when we need it. If liver injury prevents this (gluconeogenesis in the liver), you will experience low blood sugar. I am taking it as an ominous sign. I am so disheartened. For most people, this won't happen, I imagine, unless the liver stops working right. I happen to have a remote history of severe alcohol abuse and may not be working with much healthy liver tissue to begin with. I don't believe I should ever take Kava again.

Thank you for your honesty. I've personally never heard of anyone losing consciousness from kava except in the circumstance of extreme over-indulgence. Kava may not be an herb your body can process, and I say that with heavy words because we want kava to help.

Again, thank you for letting us know.

 

[PapaMoi]

Thank you for your honesty. I've personally never heard of anyone losing consciousness from kava except in the circumstance of extreme over-indulgence. Kava may not be an herb your body can process, and I say that with heavy words because we want kava to help.

Again, thank you for letting us know.

Yep. I always am sad when someone can't drink kava for whatever reason. I wish everyone could never have any negatives from it but that isn't reality for everyone.

 

[HeadHodge]

I have a liver for sale.

 

[TheKavaFlow]

I have tried Kava today, and the past 2 days as well. It has provided wonderful pain relief, but something bizarre just happened. I am also an RN. I just had this sudden, scary episode of what felt like severe hypoglycemia 2 or so hours after taking Kava. I sweated and was losing consciousness and was extremely hungry. It is resolving after much apple juice. The thing is this: Kava may not cause low blood sugar, but LIVER DAMAGE can and will cause low blood sugar. It is because the liver stores sugar for our body to use later, when we need it. If liver injury prevents this (gluconeogenesis in the liver), you will experience low blood sugar. I am taking it as an ominous sign. I am so disheartened. For most people, this won't happen, I imagine, unless the liver stops working right. I happen to have a remote history of severe alcohol abuse and may not be working with much healthy liver tissue to begin with. I don't believe I should ever take Kava again.

Hi Sean,

Might want to take a look here:
https://livertox.nih.gov/KavaKava.htm

It sounds like you're experiencing some big problems, and you probably shouldn't be consuming kava based on your reactions. The studies done by the National Institute of Health shows that any liver problems are nearly always a result of something else in that person's life rather than the kava. One key excerpt, and food for thought:

Based upon reported cases, the estimated frequency of clinically apparent liver injury due to kava is less than 1:1,000,000 daily doses.

 

[Delicate Drunk]

I have tried Kava today, and the past 2 days as well. It has provided wonderful pain relief, but something bizarre just happened. I am also an RN. I just had this sudden, scary episode of what felt like severe hypoglycemia 2 or so hours after taking Kava. I sweated and was losing consciousness and was extremely hungry. It is resolving after much apple juice. The thing is this: Kava may not cause low blood sugar, but LIVER DAMAGE can and will cause low blood sugar. It is because the liver stores sugar for our body to use later, when we need it. If liver injury prevents this (gluconeogenesis in the liver), you will experience low blood sugar. I am taking it as an ominous sign. I am so disheartened. For most people, this won't happen, I imagine, unless the liver stops working right. I happen to have a remote history of severe alcohol abuse and may not be working with much healthy liver tissue to begin with. I don't believe I should ever take Kava again.

Maybe you were just hungry and low blood sugar because you didn't eat enough. Kava suppresses appetite and so you might not have been eating like you normally do. Have you had any tests to determine whether you had a healthy liver before you started kava, or are you just worried about that?

 

[schatz]

Another overlooked reason for liver issues is iron acuummulation in the body. I was recently found to be a homozygous carrier of a gene that causes hemochromatosis and also my wife has a carrier gene for this. Very common yet overlooked, have your ferriten levels checked, many people absorb excess iron and do not ever find out about it until damage has already been done. Doctor do not run ferriten levels to check iron since 1996 so you have to do your own investigating on this one.

 

[NotKrunk]

I seriously doubt that this hypoglycemic feeling, if it was true hypoglycemia, resulted from Kava. I am not aware of Kava being implicated in Pancreatic damage. Hepatogenous diabetes can happen but this is associated with chronic liver disease. If one's liver is already fragile I would tread carefully in using anything, drugs or herbs, that may put a possible strain on it.