Nutr Cancer. 2012 Jun 13. [Epub ahead of print]Reduction in Colon Cancer Risk by Consumption of Kava or Kava Fractions in Carcinogen-Treated Rats.Triolet J, Shaik AA, Gallaher DD, O'Sullivan MG, Xing C.Sourcea Department of Food Science and Nutrition , University of Minnesota , St. Paul , Minnesota , USA.AbstractEpidemiological studies suggest that kava reduces colon cancer risk. However, no experimental studies of the chemopreventive properties of kava toward colon cancer have been reported. Further, there are concerns regardinghepatotoxicity of kava. The goal of this study was to determine whether kava consumption reduces markers of colon cancer in an animal model and to study the safety of kava. An ethanolic extract and polar and nonpolar fractions of the kava extract were fed to rats for 12 days prior to, during, and after administration of dimethylhydrazine, a colon-specific carcinogen. After 14 wk, rats fed the nonpolar extract had a significant reduction in precancerous lesions [aberrant crypt (AC) foci (ACF)] as well as large (≥4 AC/ACF) sialomucin-only expressing foci, an indicator of greater tumorigenic potential, compared to the control group. None. The combined kava groups had significantly fewer total AC, ACF, large ACF, and large sialomucin-only expressing foci compared to the control group. NoneNoneInteresting find, polar water derived kavalactones had benefits on colon cancer (ethanolic extracts too) and no hepatic lesions were found. 14 weeks of a kava diet should be enough to see if hepatotoxicity would occur. I cannot fathom for any physiological reason why it would become toxic after this period, no other hepatotoxin does this. Meaning, stay safe then become toxic, alcohol exerts acute effects that are apparent after one night in some cases. NonePhytother Res. 2012 May 14. doi: 10.1002/ptr.4729. [Epub ahead of print]Contaminant Hepatotoxins as Culprits for Kava Hepatotoxicity - Fact or Fiction?Teschke R, Sarris J, Lebot V.SourceDepartment of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Teaching Hospital of the Medical Faculty of the Goethe University of Frankfurt/ Main, Germany. [email protected] culprit of kava hepatotoxicity will continue to remain a mystery in humans, if the underlying reaction is of idiosyncratic, unpredictable, and dose-independent nature due potentially to some metabolic aberration in a few individuals emerging fromkava use.None. This led us to propose our 'working hypothesis' that contaminant hepatotoxins including moulds might have caused rare kava hepatotoxicity in humans. Further studies are now warranted to proof or disproof our working hypothesis, because kava hepatotoxicity possibly based on contaminant hepatotoxins could be a preventable disease. In the meantime, however, for minimizing toxicity risk in kava users, a pragmatic approach should focus on the medicinal use of an aqueous extract derived from peeled rhizomes and roots of a non-mouldy noble kava cultivar, limited to maximum 250-mg kavalactones daily for acute or intermittent use. Copyright © 2012 John Wiley & Sons, Ltd.
the mold and shitty kava theory again.
Food Chem Toxicol. 2011 Nov;49(11):2820-9. Epub 2011 Aug 18.Liver toxicity and carcinogenicity in F344/N rats and B6C3F1 mice exposed toKava Kava.Behl M, Nyska A, Chhabra RS, Travlos GS, Fomby LM, Sparrow BR, Hejtmancik MR, Chan PC.SourceNational Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.AbstractKava Kava is an herbal supplement used as an alternative to antianxiety drugs. Although some reports suggest an association of Kava Kava with hepatotoxicity , it continues to be used in the United States due to lack of toxicity characterization. In these studies F344/N rats and B6C3F1 mice were administered Kava Kava extract orally by gavage in corn oil for two weeks, thirteen weeks or two years. Results from prechronic studies administered Kava Kava at 0.125 to 2g/kg body weight revealed dose-related increases in liver weights and incidences of hepatocellular hypertrophy. In the chronic studies, there were dose-related increases in the incidences of hepatocellular hypertrophy in rats and mice administered Kava Kava for up to 1g/kg body weight. This was accompanied by significant increases in incidences of centrilobular fatty change. There was no treatment- related increase in carcinogenic activity in the livers of male or female rats in the chronic studies. Male mice showed a significant dose-related increase in the incidence of hepatoblastomas. In female mice, there was a significant increase in the combined incidence of hepatocellular adenoma and carcinoma in the low and mid dose groups but not in the high dose group. These findings were accompanied by several nonneoplastic hepatic lesions.some findings of hepatotoxicity, the study is fine and dandy, not sure what these mice mutations were so that may make it irrelevant. 1 G/KG Is high, so if you are a 200 pound male roughly 90kgs you would be taking in 90 grams of kava daily, A tad high for most.
Br J Clin Pharmacol. 2012 Feb;73(2):170-4. doi: 10.1111/j.1365-2125.2011.04070.x.Kava hepatotoxicity in traditional and modern use: the presumed Pacific kavaparadox hypothesis revisited.Teschke R, Sarris J, Schweitzer I.SourceDepartment of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Teaching Hospital of the Goethe University of Frankfurt/Main, Hanau, Germany. [email protected], a Pacific herb consumed worldwide for medicinal, recreational and cultural purposes, has been associated with rarehepatotoxicity, and there is currently a critical need to determine this causation. The previously proposed Pacific kavaparadox was based on the theory that kava hepatotoxicity was not observed following use of traditional aqueous extracts in the Pacific region, but was restricted to use of Western acetonic and ethanolic extracts. Subsequent cases analyzed by the World Health Organization and published case reports revealed that traditional aqueous extracts used in New Caledonia, Australia, the USA and Germany may also be hepatotoxic; thus, there is no longer a basis to sustain the previously proposed Pacific kava paradox. It appears that the primary cause of toxicity may reside in the time before the preparation of the various kava extracts, possibly attributed to poor quality of the raw material caused by mould hepatotoxins. Rigorous testing of kava raw material is urgently advised, in addition to Pan-Pacific kava manufacturing quality standards
This paper is interesting because it reviewed the effects of water based extracts which may still show liver toxicity. However, the proposal is that the raw material not kava itself is the issue. Mould hepatotoxins seem to be gaining more headway as the major factor is severe liver issues.
Chem Res Toxicol. 2011 Jul 18;24(7):992-1002. Epub 2011 May 3.Constituents in kava extracts potentially involved in hepatotoxicity: a review.Olsen LR, Grillo MP, Skonberg C.SourceDepartment of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Denmark. [email protected] kava root preparations have been consumed in the South Pacific as an apparently safe ceremonial and cultural drink for centuries. However, several reports of hepatotoxicity have been linked to the consumption of kava extracts in Western countries, where mainly ethanolic or acetonic extracts are used. The mechanism of toxicity has not been established, although several theories have been put forward. The composition of the major constituents, the kava lactones, varies according to preparation method and species of kava plant, and thus, the toxicity of the individual lactones has been tested in order to establish whether a single lactone or a certain composition of lactones may be responsible for the increased prevalence of kava-induced hepatotoxicity in Western countries. However, no such conclusion has been made on the basis of current data. Inhibition or induction of the major metabolizing enzymes, which might result in drug interactions, has also gained attention, but ambiguous results have been reported. On the basis of the chemical structures of kavaconstituents, the formation of reactive metabolites has also been suggested as an explanation of toxicity. Furthermore, skin rash is a side effect in kava consumers, which may be indicative of the formation of reactive metabolites and covalent binding to skin proteins leading to immune-mediated responses. None. Only a few studies have investigated the toxicity of the minor constituents present in kava extract, such as pipermethystine and the flavokavains, where some have been shown to display higher in vitro cytotoxicity than the lactones. To date, there remains no indisputable reason for the increased prevalence of kava-induced hepatotoxicity in Western countries.
switching back to liver toxicity inherant to kava. What i find interesting is that glutathione addition )GSH) reduces this effect. I would suggest that NAC would work even better as oral glutathione is less potent at boosting hepatic levels of reduced GSH than NAC.
Phytother Res. 2011 Mar;25(3):417-23. doi: 10.1002/ptr.3283. Epub 2010 Aug 23.Kavalactones Yangonin and Methysticin induce apoptosis in human hepatocytes (HepG2) in vitro.Tang J, Dunlop RA, Rowe A, Rodgers KJ, Ramzan I.SourceFaculty of Pharmacy, University of Sydney, NSW, Australia.AbstractWhile cases of severe kava hepatotoxicity have been reported, studies examining the toxicity of individual kavalactones are limited. The present study examined the in vitro hepatotoxicity of kavain, methysticin and yangonin on human hepatocytes (HepG2) and the possible mechanism(s) involved. Cytotoxicity was assessed using lactate dehydrogenase (LDH) and ethidium bromide (EB) assays. The mode of cell death was analysed with acridine orange/ethidium bromide dual staining with fluorescence microscopy. Glutathione oxidation was measured using the ortho-phthalaldehyde (OPT) fluorescence assay. Kavain had minimal cytotoxicity, methysticin showed moderate concentration-dependent toxicity and yangonin displayed marked toxicity with ~ 40% reduction in viability in the EB assay. Acridine orange/ethidium bromide staining showed the predominant mode of cell death was apoptosis rather than necrosis. No significant changes were observed in glutathione levels, excluding this as the primary mechanism of cell death in this model. Further studies may elucidate the precise apoptotic pathways responsible and whether toxic kavalactone metabolites are involved.
This paper however, showed no reduction in liver GSH levels, citing it as not involved in the pathogenesis of liver injury. Interesting.
Phytother Res. 2012 Apr 4. doi: 10.1002/ptr.4652. [Epub ahead of print]Pacific Island 'Awa (Kava) Extracts, but not Isolated Kavalactones, Promote Proinflammatory Responses in Model Mast Cells.Shimoda LM, Park C, Stokes AJ, Gomes HH, Turner H.SourceLaboratory of Immunology and Signal Transduction, Department of Biology, Chaminade University, Honolulu, Hawaii.AbstractKava ('Awa) is a traditional water-based beverage in Pacific island communities, prepared from the ground root and stems of Piper methysticum. Kava use is associated with an ichthyotic dermatitis and delayed type hypersensitivity reactions. In the current study we collated preparative methodologies from cultural practitioners and recreational kava users in various Pacific communities. We standardized culturally informed aqueous extraction methods and prepared extracts that were subjected to basic physicochemical analysis. Mast cells exposed to these extracts displayed robust intracellular free calcium responses, and concomitant release of proinflammatory mediators. In contrast, mast cells were refractory to single or combinatorial stimulation with kavalactones, including methysticin, dihydromethysticin and kavain. Moreover, we reproduced a traditional modification of the kava preparation methodology, pre-mixing with the mucilage of Hibiscus tiliaceus, and observed its potentiating effect on the activity of aqueous extracts in mast cells. Taken together, these data indicate that water extractable active ingredients may play a role in the physiological and pathophysiological effects of kava, and suggests that mast cell activation may be a mechanistic component of kava-related skin inflammations.
super interesting, this shows that the combo of lactones in a traditional shell actually degranulize mast cells. Mast cells are a type of white blood cell that houses inflammatory mediators involved in allergy/atopy reactions, think histamine. Thus if they are degraulated, ie opened up for simplicity you would expect to see allergic reactions just like we see (kava dermopathy). Also, it explains why some members of the board have found benedryl helpful.
J Pharmacol Sci. 2009 Nov;111(3):293-8. Epub 2009 Oct 31.Hypnotic and sleep quality-enhancing properties of kavain in sleep-disturbed rats.Tsutsui R, Shinomiya K, Takeda Y, Obara Y, Kitamura Y, Kamei C.SourceDepartment of Medicinal Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.AbstractThe present study was performed to investigate the effects of kavain on the sleep-wake cycle in comparison with that of rilmazafone and diphenhydramine using sleep-disturbed rats. Electrodes for the electroencephalogram (EEG) and electromyogram (EMG) were implanted into Wistar rats. Total awake time, non-rapid eye movement (non-REM) sleep and rapid eye movement (REM) sleep were measured for 6 h. Kavain and rilmazafone showed a significant shortening in sleep latency, decreased awake time, and increased non-REM sleep time. On the other hand, significant shortening of the sleep latency was observed following the administration of diphenhydramine, while no effects were observed on the awake and non-REM sleep time. Moreover, kavain showed a significant increase in delta activity during non-REM sleep in sleep-disturbed rats, whereas a significant decrease in delta power during non-REM sleep was observed with rilmazafone. These results clearly indicate that kavain is a compound with not only hypnotic effects, but also sleep quality-enhancement effects.
Kavain improves sleep quality, unlike other sleep aids. Nice.
Mol Pharmacol. 2008 Jun;73(6):1785-95. Epub 2008 Mar 11.Kavalactones protect neural cells against amyloid beta peptide-induced neurotoxicity via extracellular signal-regulated kinase 1/2-dependent nuclear factor erythroid 2-related factor 2 activation.Wruck CJ, Götz ME, Herdegen T, Varoga D, Brandenburg LO, Pufe T.SourceDepartment of Anatomy and Cell Biology, RWTH Aachen, Wendlingweg 2, 52074 Aachen, Germany. [email protected] hallmark of Alzheimer's disease is the accumulation of amyloid beta-peptide (AP), which can initiate a cascade of oxidative events that may result in neuronal death. Because nuclear factor erythroid 2-related factor 2 (Nrf2) is the major regulator for a battery of genes encoding detoxifying and antioxidative enzymes via binding to the antioxidant response element (ARE), it is of great interest to find nontoxic activators of Nrf2 rendering neuronal cells more resistant to AP toxicity. Using ARE-luciferase assay and Western blot, we provide evidence that the kavalactones methysticin, kavain, and yangonin activate Nrf2 time- and dose-dependently in neural PC-12 and astroglial C6 cells and thereby up-regulate cytoprotective genes. Viability and cytotoxicity assays demonstrate that Nrf2 activation is able to protect neural cells from amyloid beta-(1-42) induced neurotoxicity. Down-regulation of Nrf2 by small hairpin RNA as well as extracellular signal-regulated kinase 1/2 inhibition abolishes cytoprotection. We further give evidence that kavalactone-mediated Nrf2 activation is not dependent on oxidative stress production. Our results demonstrate that kavalactones attenuate amyloid beta-peptide toxicity by inducing protective gene expression mediated by Nrf2 activation in vitro. These findings indicate that the use of purified kavalactones might be considered as an adjunct therapeutic strategy to combat neural demise in Alzheimer disease and other oxidative stress-related diseases.
neuroprotectant? i would think so based on it's activity in the brain, but inhibition of Beta amyloid plaques is legit. It's not direct in effect, kava simply activates genes which do the work.
I'll go at more later
the mold and shitty kava theory again.
Food Chem Toxicol. 2011 Nov;49(11):2820-9. Epub 2011 Aug 18.Liver toxicity and carcinogenicity in F344/N rats and B6C3F1 mice exposed toKava Kava.Behl M, Nyska A, Chhabra RS, Travlos GS, Fomby LM, Sparrow BR, Hejtmancik MR, Chan PC.SourceNational Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.AbstractKava Kava is an herbal supplement used as an alternative to antianxiety drugs. Although some reports suggest an association of Kava Kava with hepatotoxicity , it continues to be used in the United States due to lack of toxicity characterization. In these studies F344/N rats and B6C3F1 mice were administered Kava Kava extract orally by gavage in corn oil for two weeks, thirteen weeks or two years. Results from prechronic studies administered Kava Kava at 0.125 to 2g/kg body weight revealed dose-related increases in liver weights and incidences of hepatocellular hypertrophy. In the chronic studies, there were dose-related increases in the incidences of hepatocellular hypertrophy in rats and mice administered Kava Kava for up to 1g/kg body weight. This was accompanied by significant increases in incidences of centrilobular fatty change. There was no treatment- related increase in carcinogenic activity in the livers of male or female rats in the chronic studies. Male mice showed a significant dose-related increase in the incidence of hepatoblastomas. In female mice, there was a significant increase in the combined incidence of hepatocellular adenoma and carcinoma in the low and mid dose groups but not in the high dose group. These findings were accompanied by several nonneoplastic hepatic lesions.some findings of hepatotoxicity, the study is fine and dandy, not sure what these mice mutations were so that may make it irrelevant. 1 G/KG Is high, so if you are a 200 pound male roughly 90kgs you would be taking in 90 grams of kava daily, A tad high for most.
Br J Clin Pharmacol. 2012 Feb;73(2):170-4. doi: 10.1111/j.1365-2125.2011.04070.x.Kava hepatotoxicity in traditional and modern use: the presumed Pacific kavaparadox hypothesis revisited.Teschke R, Sarris J, Schweitzer I.SourceDepartment of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Teaching Hospital of the Goethe University of Frankfurt/Main, Hanau, Germany. [email protected], a Pacific herb consumed worldwide for medicinal, recreational and cultural purposes, has been associated with rarehepatotoxicity, and there is currently a critical need to determine this causation. The previously proposed Pacific kavaparadox was based on the theory that kava hepatotoxicity was not observed following use of traditional aqueous extracts in the Pacific region, but was restricted to use of Western acetonic and ethanolic extracts. Subsequent cases analyzed by the World Health Organization and published case reports revealed that traditional aqueous extracts used in New Caledonia, Australia, the USA and Germany may also be hepatotoxic; thus, there is no longer a basis to sustain the previously proposed Pacific kava paradox. It appears that the primary cause of toxicity may reside in the time before the preparation of the various kava extracts, possibly attributed to poor quality of the raw material caused by mould hepatotoxins. Rigorous testing of kava raw material is urgently advised, in addition to Pan-Pacific kava manufacturing quality standards
This paper is interesting because it reviewed the effects of water based extracts which may still show liver toxicity. However, the proposal is that the raw material not kava itself is the issue. Mould hepatotoxins seem to be gaining more headway as the major factor is severe liver issues.
Chem Res Toxicol. 2011 Jul 18;24(7):992-1002. Epub 2011 May 3.Constituents in kava extracts potentially involved in hepatotoxicity: a review.Olsen LR, Grillo MP, Skonberg C.SourceDepartment of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Denmark. [email protected] kava root preparations have been consumed in the South Pacific as an apparently safe ceremonial and cultural drink for centuries. However, several reports of hepatotoxicity have been linked to the consumption of kava extracts in Western countries, where mainly ethanolic or acetonic extracts are used. The mechanism of toxicity has not been established, although several theories have been put forward. The composition of the major constituents, the kava lactones, varies according to preparation method and species of kava plant, and thus, the toxicity of the individual lactones has been tested in order to establish whether a single lactone or a certain composition of lactones may be responsible for the increased prevalence of kava-induced hepatotoxicity in Western countries. However, no such conclusion has been made on the basis of current data. Inhibition or induction of the major metabolizing enzymes, which might result in drug interactions, has also gained attention, but ambiguous results have been reported. On the basis of the chemical structures of kavaconstituents, the formation of reactive metabolites has also been suggested as an explanation of toxicity. Furthermore, skin rash is a side effect in kava consumers, which may be indicative of the formation of reactive metabolites and covalent binding to skin proteins leading to immune-mediated responses. None. Only a few studies have investigated the toxicity of the minor constituents present in kava extract, such as pipermethystine and the flavokavains, where some have been shown to display higher in vitro cytotoxicity than the lactones. To date, there remains no indisputable reason for the increased prevalence of kava-induced hepatotoxicity in Western countries.
switching back to liver toxicity inherant to kava. What i find interesting is that glutathione addition )GSH) reduces this effect. I would suggest that NAC would work even better as oral glutathione is less potent at boosting hepatic levels of reduced GSH than NAC.
Phytother Res. 2011 Mar;25(3):417-23. doi: 10.1002/ptr.3283. Epub 2010 Aug 23.Kavalactones Yangonin and Methysticin induce apoptosis in human hepatocytes (HepG2) in vitro.Tang J, Dunlop RA, Rowe A, Rodgers KJ, Ramzan I.SourceFaculty of Pharmacy, University of Sydney, NSW, Australia.AbstractWhile cases of severe kava hepatotoxicity have been reported, studies examining the toxicity of individual kavalactones are limited. The present study examined the in vitro hepatotoxicity of kavain, methysticin and yangonin on human hepatocytes (HepG2) and the possible mechanism(s) involved. Cytotoxicity was assessed using lactate dehydrogenase (LDH) and ethidium bromide (EB) assays. The mode of cell death was analysed with acridine orange/ethidium bromide dual staining with fluorescence microscopy. Glutathione oxidation was measured using the ortho-phthalaldehyde (OPT) fluorescence assay. Kavain had minimal cytotoxicity, methysticin showed moderate concentration-dependent toxicity and yangonin displayed marked toxicity with ~ 40% reduction in viability in the EB assay. Acridine orange/ethidium bromide staining showed the predominant mode of cell death was apoptosis rather than necrosis. No significant changes were observed in glutathione levels, excluding this as the primary mechanism of cell death in this model. Further studies may elucidate the precise apoptotic pathways responsible and whether toxic kavalactone metabolites are involved.
This paper however, showed no reduction in liver GSH levels, citing it as not involved in the pathogenesis of liver injury. Interesting.
Phytother Res. 2012 Apr 4. doi: 10.1002/ptr.4652. [Epub ahead of print]Pacific Island 'Awa (Kava) Extracts, but not Isolated Kavalactones, Promote Proinflammatory Responses in Model Mast Cells.Shimoda LM, Park C, Stokes AJ, Gomes HH, Turner H.SourceLaboratory of Immunology and Signal Transduction, Department of Biology, Chaminade University, Honolulu, Hawaii.AbstractKava ('Awa) is a traditional water-based beverage in Pacific island communities, prepared from the ground root and stems of Piper methysticum. Kava use is associated with an ichthyotic dermatitis and delayed type hypersensitivity reactions. In the current study we collated preparative methodologies from cultural practitioners and recreational kava users in various Pacific communities. We standardized culturally informed aqueous extraction methods and prepared extracts that were subjected to basic physicochemical analysis. Mast cells exposed to these extracts displayed robust intracellular free calcium responses, and concomitant release of proinflammatory mediators. In contrast, mast cells were refractory to single or combinatorial stimulation with kavalactones, including methysticin, dihydromethysticin and kavain. Moreover, we reproduced a traditional modification of the kava preparation methodology, pre-mixing with the mucilage of Hibiscus tiliaceus, and observed its potentiating effect on the activity of aqueous extracts in mast cells. Taken together, these data indicate that water extractable active ingredients may play a role in the physiological and pathophysiological effects of kava, and suggests that mast cell activation may be a mechanistic component of kava-related skin inflammations.
super interesting, this shows that the combo of lactones in a traditional shell actually degranulize mast cells. Mast cells are a type of white blood cell that houses inflammatory mediators involved in allergy/atopy reactions, think histamine. Thus if they are degraulated, ie opened up for simplicity you would expect to see allergic reactions just like we see (kava dermopathy). Also, it explains why some members of the board have found benedryl helpful.
J Pharmacol Sci. 2009 Nov;111(3):293-8. Epub 2009 Oct 31.Hypnotic and sleep quality-enhancing properties of kavain in sleep-disturbed rats.Tsutsui R, Shinomiya K, Takeda Y, Obara Y, Kitamura Y, Kamei C.SourceDepartment of Medicinal Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.AbstractThe present study was performed to investigate the effects of kavain on the sleep-wake cycle in comparison with that of rilmazafone and diphenhydramine using sleep-disturbed rats. Electrodes for the electroencephalogram (EEG) and electromyogram (EMG) were implanted into Wistar rats. Total awake time, non-rapid eye movement (non-REM) sleep and rapid eye movement (REM) sleep were measured for 6 h. Kavain and rilmazafone showed a significant shortening in sleep latency, decreased awake time, and increased non-REM sleep time. On the other hand, significant shortening of the sleep latency was observed following the administration of diphenhydramine, while no effects were observed on the awake and non-REM sleep time. Moreover, kavain showed a significant increase in delta activity during non-REM sleep in sleep-disturbed rats, whereas a significant decrease in delta power during non-REM sleep was observed with rilmazafone. These results clearly indicate that kavain is a compound with not only hypnotic effects, but also sleep quality-enhancement effects.
Kavain improves sleep quality, unlike other sleep aids. Nice.
Mol Pharmacol. 2008 Jun;73(6):1785-95. Epub 2008 Mar 11.Kavalactones protect neural cells against amyloid beta peptide-induced neurotoxicity via extracellular signal-regulated kinase 1/2-dependent nuclear factor erythroid 2-related factor 2 activation.Wruck CJ, Götz ME, Herdegen T, Varoga D, Brandenburg LO, Pufe T.SourceDepartment of Anatomy and Cell Biology, RWTH Aachen, Wendlingweg 2, 52074 Aachen, Germany. [email protected] hallmark of Alzheimer's disease is the accumulation of amyloid beta-peptide (AP), which can initiate a cascade of oxidative events that may result in neuronal death. Because nuclear factor erythroid 2-related factor 2 (Nrf2) is the major regulator for a battery of genes encoding detoxifying and antioxidative enzymes via binding to the antioxidant response element (ARE), it is of great interest to find nontoxic activators of Nrf2 rendering neuronal cells more resistant to AP toxicity. Using ARE-luciferase assay and Western blot, we provide evidence that the kavalactones methysticin, kavain, and yangonin activate Nrf2 time- and dose-dependently in neural PC-12 and astroglial C6 cells and thereby up-regulate cytoprotective genes. Viability and cytotoxicity assays demonstrate that Nrf2 activation is able to protect neural cells from amyloid beta-(1-42) induced neurotoxicity. Down-regulation of Nrf2 by small hairpin RNA as well as extracellular signal-regulated kinase 1/2 inhibition abolishes cytoprotection. We further give evidence that kavalactone-mediated Nrf2 activation is not dependent on oxidative stress production. Our results demonstrate that kavalactones attenuate amyloid beta-peptide toxicity by inducing protective gene expression mediated by Nrf2 activation in vitro. These findings indicate that the use of purified kavalactones might be considered as an adjunct therapeutic strategy to combat neural demise in Alzheimer disease and other oxidative stress-related diseases.
neuroprotectant? i would think so based on it's activity in the brain, but inhibition of Beta amyloid plaques is legit. It's not direct in effect, kava simply activates genes which do the work.
I'll go at more later
