To determine whether such nuclear receptors may fujction Forskolin and liver function FSK effects ans BC formation and gene regulation Blackberry and cream cheese stuffed French toast HepaRG cell cultures, we Antidepressant for insomnia HepaRG cells by DDF, a structural analogue of FSK activating PXR, Forskilin not adenylate cyclase 31 Foorskolin, and by rifampicin and GW, reference agonists of PXR and FXR, respectively Blood pressure was assessed in the supine position after resting for 5-min with a mercurial sphygmomanometer Trimline by PyMah Corporation, Somerville, NJ using standard procedures. Article CAS PubMed Google Scholar Enserink, J. Nature Restore. She recovered after a liver transplant [ 24 ]. But since their effects may be different in humans, we recommend avoiding this herb altogether, especially if you already have liver problems [ 6 ].

Forskolin and liver function -

Interestingly, DDF and rifampicin, unlike GW, were found to trigger BC formation in HepaRG cells, but to a lower extent than FSK Fig. They also enhanced CYP3A4 mRNA expression, as expected for PXR agonists, but failed to increase, or only weakly induced, other hepatic markers such as NTCP, OATP2B1, G6P and BSEP Fig.

GW was found to induce mRNA expression of the reference FXR target BSEP Fig. Formation of BC and hepatic marker mRNA expression in HepaRG cells exposed to the PXR agonists DDF or rifampicin or to the FXR agonist GW To further analyze the possible implication of PXR in FSK polarizing activity, we studied the effect of siRNA-mediated PXR silencing on FSK effects in HepaRG cells.

The efficiency of the siRNA-mediated approach was demonstrated by its capacity to decrease PXR protein expression Supplementary Fig. S5a and to hinder FSK-mediated CYP3A4 up-regulation Supplementary Fig. S5b in HepaRG cells. SiRNA-mediated depletion of PXR was found to markedly reduce BC formation due to FSK treatment, without however fully abolishing it Fig.

It however failed to alter G6P up-regulation due to FSK Supplementary Fig. PXR role in FSK-mediated BC formation was further studied using PXR-KO HepaRG cells and corresponding control F5 HepaRG cells PXR-KO cells failed to express PXR as demonstrated by Western-blotting Supplementary Fig.

S5a ; they did not exhibit FSK-mediated up-regulation of CYP3A4 mRNA, whereas that of G6P was preserved Supplementary Fig. FSK-mediated BC formation was found to be nearly fully abrogated in PXR-KO HepaRG cells, but occurred in control F5 cells Fig.

When cultured for 18 days at confluency in basal conditions absence of FSK and of DMSO , PXR-KO HepaRG cells were however able to spontaneously develop BC structures Fig.

Such data suggest that PXR may be required for BC formation triggered by FSK, but not by confluency time, in HepaRG cells. Effects of PXR silencing on FSK-induced formation of BC. a , b Untransfected UNT and SiNT- or SiPXR-transfected HepaRG cells as well as PXR-KO and control F5 HepaRG clone cells were either exposed to 0.

d The biliary markers P-gp and MRP2 were immunolocalized, as described in Methods; specific immunolabelling appears as green fluorescence on fluorescence microscopy pictures, whereas DAPI-stained nuclei are blue; BC-associated green fluorescence is indicated by white arrows; the data shown are representative of three independent assays.

Indeed, FSK treatment triggers the appearance of BC structures, expressing biliary markers like the efflux pumps P-gp and MRP2.

Moreover, these BC appear to be functional, as demonstrated by the secretion of the MRP2 substrate CF into their lumen. Such data therefore confirm the fact that FSK can act as a polarizing agent for hepatocytes, as already described for rat hepatocytes and human HepG2 cells 18 , However, for HepG2 cells, in contrast to HepaRG cells, BC structures are likely difficult to detect by phase-contrast microscopy and mislocalization of apical markers may occur In addition to stimulate polarization, FSK unambiguously increased mRNA expression of hepatic markers in HepaRG cells, notably those of the drug metabolizing enzymes CYP3A4 and UGT1A1, the drug transporters NTCP, OATP2B1 and BSEP and the glucose metabolism enzymes aldolase B and G6P.

FSK concomitantly robustly induced CYP3A4 activity and NTCP and OATP activity. In contrast, expression of the biliary marker cytokeratin 19 was decreased.

Such data suggest that FSK may act as a global differentiating agent towards HepaRG cells, through favoring the acquisition of key hallmarks of the differentiated hepatocyte, like a polarized status and the expression of hepatic enzymes involved in drug or carbohydrate metabolism.

Such differentiation features are similarly promoted by treating HepaRG cells with DMSO 1 , 6. In this context, it is however noteworthy that FSK failed to recapitulate all the differentiating effects of DMSO.

The profile of hepatic differentiation in FSK-treated HepaRG cells is therefore only partly identical to that found in DMSO-treated counterparts.

The fact that mRNA expression of the canalicular marker BSEP was markedly induced by FSK, but not by DMSO, supports this conclusion.

FSK is primarily known to basically stimulate the production of cAMP through adenylate cyclase activation 14 , FSK has more recently been shown to activate other targets such as the receptors PXR and FXR 31 , Interestingly, this multifaceted activity of FSK is most likely involved in its polarizing and differentiating effects towards HepaRG cells.

Indeed, various cAMP analogs, like FSK, were shown to stimulate expression of some hepatic markers, such as NTCP, OATP2B1 and G6P, in HepaRG cells. They additionally partly favored the development of BC.

The phosphodiesterase inhibitor IBMX, known to indirectly raised intracellular cAMP levels, also partly stimulated BC formation in HepaRG cells, thus confirming the link between cAMP levels and HepaRG cell polarization. In the same way, PXR agonists, like rifampicin and DDF, a FSK analog devoid of adenylate cyclase activation property 31 , partially promoted the formation of BC; they additionally enhanced the expression of CYP3A4, well-known to be a reference PXR target The involvement of PXR in polarizing effects of FSK is also supported by the fact that FSK-mediated BC formation and CYP3A4 up-regulation in HepaRG cells were impaired by PXR depletion, achieved transiently through siRNA-transfection or stably through the use of PXR-KO HepaRG cells.

The FXR agonist GW was additionally shown to induce BSEP expression, like FSK, without however stimulating BC development. Polarizing and differentiating effects of FSK towards HepaRG cells may therefore reflect its combined effects on cAMP level and PXR- and FXR-signaling ways See Fig.

This hypothesis is supported by the fact that co-treatment by the cAMP analog Sp-DCl-cBIMPS and rifampicin fully reproduced the polarizing and differentiating effects of FSK, except for the up-regulation of BSEP, most likely due to FSK-mediated FXR activation. Schematic representation of the signaling ways that may contribute to the FSK effects in HepaRG cells.

The exact signaling ways by which cAMP and PXR promote BC formation in HepaRG cells remain to be determined. The role of main cAMP-downstream effectors, Epac and PKA, were analyzed by using specific cAMP analogs.

A contribution of PKA may have consequently to be considered, without, however, formally discarding non-canonical cAMP-related ways, described in various cell lines 37 , 38 , 39 , 40 and implicating diverse emergent cAMP effectors proteins, such as cyclic-nucleotide gated channels 41 , Popeye domain containing proteins 42 or the cAMP sensor Rapgef2 With respect to PXR, it is most likely involved in FSK-mediated up-regulation of CYP3A4 in HepaRG cells, through transcriptionally activating this reference PXR target gene The contribution of PXR to polarizing effects of FSK seems to be more complex to apprehend.

Indeed, if PXR appears to be at least partly required for FSK-mediated formation of BC in HepaRG cells, its absence in PXR-KO HepaRG cells did not preclude the polarization of these cells with confluency time, indicating that BC formation may arise in the absence of PXR.

The fact that alteration of BC has not been reported in the liver of Pxr-KO mouse supports this conclusion 44 , In the same way, the effects of PXR towards hepatic differentiation of hESC are complex; thus, microbial-derived lithocholic acid and vitamin K2 have been reported to drive PXR-dependent metabolic maturation of hESC-derived hepatocytes 46 , whereas, by contrast, stable overexpression of PXR in hepatic-induced hESCs failed to enhance expression of hepatic phenotype marker Additional studies are therefore welcome to precise how activation of PXR may contribute to BC formation in FSK-exposed HepaRG cells and, beyond, to define the exact role of PXR in hepatic polarization and differentiation processes.

Nevertheless, our data, through supporting a function for PXR in BC formation, reinforce the conclusion that PXR exerts pleiotropic roles in cellular metabolism and physiology, apart from that initially devoted to drug detoxification pathway regulation 47 , 48 , The HepaRG cell line is now well-recognized as an original and convenient in vitro model for pharmacological and toxicological studies, acting as a surrogate for primary cultures of human hepatocytes 4 , 5 , 6.

The use of HepaRG cells may however be hampered by the necessity of adding the non-physiological and potentially toxic agent DMSO in culture medium during a relative long culture time 14 days for getting differentiated cells.

In this context, the alternative use of FSK-treated HepaRG cells may be interesting to consider as it permits to discard DMSO and to obtain polarized cells after a short-time treatment 3 days , if done with high density-plated cells.

Moreover, these FSK-treated HepaRG cells exhibit various hepatic differentiated features, including expression of CYP3A4 and drug transporters like NTCP, OATP2B1, MRP2 and BSEP, even if other hepatic markers like CYP1A2, CYP2E1 and CAR remain at levels much lower than those found in DMSO-treated counterparts, as already discussed above.

Additional works are needed to determine the potential relevance of FSK-treated HepaRG cells as an in vitro model for pharmacological-toxicological studies and also to improve it with respect to expression of some hepatic markers.

In summary, FSK was shown to polarize and differentiate human hepatoma HepaRG cells, without the addition of DMSO. This most likely occurs through mobilization of the multifaceted activities of the diterpene, i.

Such effects of FSK may help to ameliorate the use of HepaRG cells as surrogates for human hepatocytes in in vitro hepatic studies and also suggest a previously-unrecognized putative role for PXR in hepatocyte polarization.

Gripon, P. et al. Infection of a human hepatoma cell line by hepatitis B virus. Article ADS CAS PubMed Google Scholar. Aninat, C. Expression of cytochromes P, conjugating enzymes and nuclear receptors in human hepatoma HepaRG cells. Article CAS PubMed Google Scholar.

Le Vee, M. Polarized expression of drug transporters in differentiated human hepatoma HepaRG cells.

Guillouzo, A. The human hepatoma HepaRG cells: a highly differentiated model for studies of liver metabolism and toxicity of xenobiotics. Andersson, T. The HepaRG cell line: a unique in vitro tool for understanding drug metabolism and toxicology in human. Antherieu, S. Optimization of the HepaRG cell model for drug metabolism and toxicity studies.

Nikolaou, N. Optimizing human hepatocyte models for metabolic phenotype and function: effects of treatment with dimethyl sulfoxide DMSO. Article Google Scholar.

Hoekstra, R. The HepaRG cell line is suitable for bioartificial liver application. Nibourg, G. Liver progenitor cell line HepaRG differentiated in a bioartificial liver effectively supplies liver support to rats with acute liver failure.

Article ADS CAS PubMed PubMed Central Google Scholar. Rebelo, S. HepaRG microencapsulated spheroids in DMSO-free culture: novel culturing approaches for enhanced xenobiotic and biosynthetic metabolism.

van Wenum, M. Oxygen drives hepatocyte differentiation and phenotype stability in liver cell lines. Article PubMed PubMed Central Google Scholar. Chen, F. The human constitutive androstane receptor promotes the differentiation and maturation of hepatic-like cells. van der Mark, V. Stable overexpression of the constitutive androstane receptor reduces the requirement for culture with dimethyl sulfoxide for high drug metabolism in HepaRG cells.

Seamon, K. Forskolin: unique diterpene activator of adenylate cyclase in membranes and in intact cells. Proc Natl Acad Sci USA 78 , — Article ADS CAS Google Scholar. Sapio, L. The natural cAMP elevating compound forskolin in cancer therapy: Is it time? Ranta, T.

Wice, B. Modulators of cyclic AMP metabolism induce syncytiotrophoblast formation in vitro. Exp Cell Res , — Article CAS Google Scholar.

Fu, D. Regulation of bile canalicular network formation and maintenance by AMP-activated protein kinase and LKB1. Article CAS PubMed PubMed Central Google Scholar. Zegers, M. Sphingolipid transport to the apical plasma membrane domain in human hepatoma cells is controlled by PKC and PKA activity: a correlation with cell polarity in HepG2 cells.

J Cell Biol , — Ogawa, S. Three-dimensional culture and cAMP signaling promote the maturation of human pluripotent stem cell-derived hepatocytes. Burbank, M. Schneider, C. NIH Image to ImageJ: 25 years of image analysis.

Nat Methods 9 , — Regulation of drug transporter expression in human hepatocytes exposed to the proinflammatory cytokines tumor necrosis factor-alpha or interleukin Lecureur, V.

ERK-dependent induction of TNFalpha expression by the environmental contaminant benzo a pyrene in primary human macrophages. Jigorel, E. Functional expression of sinusoidal drug transporters in primary human and rat hepatocytes.

Bradford, M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.

Anal Biochem 72 , — Payen, L. Characterization and inhibition by a wide range of xenobiotics of organic anion excretion by primary human hepatocytes. Biochem Pharmacol 60 , — Poppe, H. Cyclic nucleotide analogs as probes of signaling pathways.

Enserink, J. A novel Epac-specific cAMP analogue demonstrates independent regulation of Rap1 and ERK. Essayan, D. Al-Azhar Journal of Pharmaceutical Sciences , 51 1 , doi: Nermeen El-Agroudy. Al-Azhar Journal of Pharmaceutical Sciences , 51, 1, , Al-Azhar Journal of Pharmaceutical Sciences , ; 51 1 : Toggle navigation.

Mistletoe Viscum album has been reported to cause liver injury increased levels of the markers AST and ALT and hepatitis in several people [ 52 , 53 , 54 ]. In South Africa, impila Callilepis laureola has been associated with some cases of hepatitis and kidney damage. In one case, a mother who consumed impila died of liver necrosis.

Valerian is usually safe when taken at typical doses for weeks. However, some compounds in valerian are toxic and can cause cell damage.

Avoid long-term use and high doses [ 57 ]. Not many studies speak to its liver-damaging effects. Still, there are enough data to recommend against it in people with liver problems. In one patient, valerian caused acute hepatitis.

In others, it caused liver damage. Lastly, high doses of valerian oil had toxic effects on rat liver and cultured hepatoma cells in one lab experiment [ 58 , 24 , 59 , 60 ]. Liver damage has been reported in a few people taking black cohosh Actaea racemosa.

However, a meta-analysis concluded that there is no such evidence that it harms the liver [ 61 ]. According to one study, two women developed acute liver necrosis after taking black cohosh [ 62 ].

In another case study, a year-old woman developed liver injury within a month of using black cohosh to resolve her hot flashes [ 63 ]. These cases are uncommon. Saw palmetto Serenoa repens preparations have caused cholestatic hepatitis in some patients [ 64 ]. One man, a former alcoholic, developed acute hepatitis and pancreatitis after taking the herb.

In another case report, saw palmetto caused sudden liver damage [ 65 , 66 ]. Although the evidence is sparse, it might also be toxic to the liver.

His condition progressed to liver failure [ 67 ]. A year-old man suffered from acute cholestatic hepatitis induced by corydalis Corydalis speciosa Max. He complained of jaundice and a mild abdominal discomfort [ 68 ]. One patient had a transient increase in liver transaminase activity after using calcium sodium EDTA.

The toxicity resolved after its discontinuation [ 69 , 70 ]. Consumption of large amounts of yerba mate tea over a period of years caused liver disease in one young woman [ 71 , 72 ]. A year-old woman developed acute liver failure from regularly drinking tea containing senna Cassia angustifolia.

The toxic effects of senna are ascribed to its major constituents, sennosides [ 73 ]. Nutmeg Myristica fragrans was toxic to the liver in mice with liver damage and has also been reported to cause hepatotoxicity and anxiety in an year-old student who used it for recreational purposes [ 74 , 75 ].

Ingestion of clove oil resulted in coma, fits, blood clotting issues, and acute liver damage in a 2-year-old boy [ 76 ]. Coltsfoot is a plant of the daisy family commonly used in folk medicine for lung problems.

A baby developed reversible liver disease after being given coltsfoot tea, possibly due to its pyrrolizidine alkaloids [ 77 ]. Based on animal studies, coltsfoot is likely safe in adults at typical doses.

Exercise some caution when using it, though [ 78 ]. Borage Borago officinalis seed oil has complex molecules called pyrrolizidine alkaloids, which are toxic to the liver.

Their concentration must be lower than ppt or 0. However, no liver toxicity cases from taking borage seed oil have been reported [ 79 , 80 ]. Pennyroyal Mentha pulegium oil is also called spraw mint. It is said to be highly toxic, and animal studies have reported its toxicity to the liver — possibly due to the presence of pulegone, a highly poisonous compound [ 81 ].

Forskolin has some potential benefits such as increasing energy levels and promoting weight loss , but may cause liver damage. At 2 — 3 times the recommended human dose, peppermint oil Mentha× piperita could be toxic to liver cells [ 60 , 83 ]. Chronic treatment with peppermint oil resulted in some degree of liver impairment in animals, although no other parameters of liver function were impaired [ 84 ].

In one study, high doses of peppermint oil increased bile and markers of liver damage ALT on rat liver and cultured human liver cells over a long period of time [ 60 ].

Olive leaf extract is very safe in general. However, high doses induced liver changes in mice [ 86 , 87 ]. The following compounds are found in some foods and supplements, being responsible for some of the liver toxicity cases previously mentioned. Coumarin is a natural substance found in many plants.

At high doses, coumarin causes liver damage in rats and mice [ 88 ]. European health agencies have warned against high consumption of Cassia cinnamon bark due to its high coumarin content [ 89 ].

Coumarin is found naturally in various other edible plants like strawberries, black currants, apricots, and cherries. Its levels in these fruits are practically negligible, though [ 90 ].

Journal of the International Society of Sports Nutrition Meal planning for diabetics ForakolinArticle number: 54 Cite wnd article. Metrics details. Funxtion study investigated the effects of Coleus Forskohlii CF on body composition, and determined the safety and efficacy of supplementation. Fasting blood samples and dietary records 4-d were obtained at 0 and wks. Side effects were recorded on a weekly basis.

Coleus Fkrskolin root extract Frskolin represented by znd bioactive constituent 'forskolin' Meal planning for diabetics popularly used as Forskoliin natural weight-lowering product, but Grape Vineyard Sustainability Practices association of its use with liver-related risks is very limited.

Food Forsmolin, body weights, relative organ weights an liver marker enzymes [aspartate aminotransferase Functionnalanine Non-prescription weight loss pills ALTand alkaline phosphatase ALP ] combined with histophatological analysis lievr assessed.

CFE funtcion The extract 0. The Forskoli effect Meal planning for diabetics throughout the 3-weeks course but was restored towards normalization within 1 week after withdrawal of treatment. Liver histology of mice fed 0. In contrast, none of the hepatic responses measured were altered when mice were given a diet containing pure forskolin alone at the dose corresponding to its content in 0.

The present study clearly indicated that forskolin was not involved in the CFE-induced hepatotoxicity and was caused by other unidentified constituents in CFE which warrants further studies. Keywords: Coleus forskohlii; fatty liver; forskolin; hepatotoxicity; liver marker enzymes; visceral fat.

Abstract Coleus forskohlii root extract CFE represented by its bioactive constituent 'forskolin' is popularly used as a natural weight-lowering product, but the association of its use with liver-related risks is very limited. Publication types Research Support, Non-U.

Substances Biomarkers Plant Extracts Colforsin Aspartate Aminotransferases Alanine Transaminase Alkaline Phosphatase.

: Forskolin and liver function

Similar items that may ship from close to you	The following compounds are found in some foods and supplements, being responsible for some of the liver toxicity cases previously mentioned. These analyzers were calibrated daily to controls according to manufacturer recommendations and federal guidelines for clinical diagnostic laboratories. View author publications. Effects of Coleus Forskohlii Supplementation on Body Composition and Hematological Profiles in Mildly Overweight Women. The following discusses the results of this study in greater detail. Download references. These hematological responses were measured for the analysis of the safety of the supplement on general markers of health.
37 Supplements & Foods that May Be Bad for Your Liver - SelfDecode Health	doi: Nermeen El-Agroudy. Al-Azhar Journal of Pharmaceutical Sciences , 51, 1, , Al-Azhar Journal of Pharmaceutical Sciences , ; 51 1 : Toggle navigation. Home Browse Current Issue By Issue By Author By Subject Author Index Keyword Index Journal Info About Journal Aims and Scope Editorial Board Publication Ethics Peer Review Process Guide for Authors Submit Manuscript Contact Us Login Register. Calculators Molarity. Mass picograms nanograms micrograms milligrams grams kilograms. Concentration femtomolar picomolar nanomolar micromolar millimolar molar. Volume nanoliter microliter milliliter liter. Concentration 1 femtomolar picomolar nanomolar micromolar millimolar molar. Volume 1 nanoliter microliter milliliter liter. Concentration 2 femtomolar picomolar nanomolar micromolar millimolar molar. Volume 2 nanoliter microliter milliliter liter. Chemical name [3 R - 3 H -naphtho[2,1- b ]pyranone. Molecular Weight Chemical structure. Molecular Formula C 22 H 34 O 7. CAS Number PubChem identifier MDL number MFCD Technical guides Understanding purity and quality - a guide for life scientists The role of small molecules in stem cell biology. References for Forskolin. References are publications that support the biological activity of the product. Forskolin and derivatives as tools for studying the role of cAMP. Alasbahi RH et al Pharmazie 67 1 : Read more PubMedID: Wagh VD et al J Postgrad Med 58 3 : Insel PA et al Cell Mol Neurobiol 23 3 : Awad JA et al J Biol Chem 5 : Submit Yours Now. These publications cite the use of Forskolin purchased from Hello Bio:. In vitro modelling of human microglial alterations associated with Alzheimer's disease and polygenic risk Salis et al Cardiff University : Thesis. Singleton S et al Br J Pharmacol 8 : PubMedID: Condon AF et al Cell Rep 36 5 : PubMedID: Ahmad et al Cells 10 5 : Items 1 to 5 of 9 total Page You're currently reading page 1 Page 2 Page Next. Related Products. Add to Wish List Add to Compare. About you First Name:. Last Name:. Barthélemy St. Helena St. Lucia St. The processed roots of fo-ti might be less toxic, according to animal studies. But since their effects may be different in humans, we recommend avoiding this herb altogether, especially if you already have liver problems [ 6 ]. Cassia Cinnamon Cinnamomum cassia is Chinese cinnamon. It has higher quantities of coumarin compared to the regular, Ceylon cinnamon. Taking in too much of this herb can cause liver damage [ 7 , 8 ]. The German Federal Institute for Risk Assessment warned against consuming large amounts of Cassia cinnamon in According to one study, three women 61, 52 and 49 years old developed jaundice after taking gotu kola. All of them improved after stopping this supplement. Gotu kola also induced liver toxicity in one child [ 9 , 10 ]. Hepatitis and cirrhosis have also been reported. Avoid this herb or use it with extreme caution [ 11 ]. High doses or prolonged ingestion of even moderate amounts of vitamin A may cause liver damage [ 12 , 13 ]. Long-term or high doses of niacin time-release preparations have led to liver failure or hepatotoxicity in some people. High doses of beta-carotene worsened alcohol-induced liver injury in rats, while lower doses were protective [ 16 ]. To sum it up, most vitamins are not harmful in normal doses. Avoid megadoses, especially of niacin and beta-carotene. Chaparral is a shrub that grows in California and Mexico. In one study, patients taking chaparral suffered acute to chronic irreversible liver damage with sudden liver failure [ 18 , 19 ]. One review reported 18 toxicity cases after ingesting chaparral, with jaundice as the main sign of liver disease [ 20 ]. In the US, kava kava is usually sold as pills. These pills may contain various toxic solvents. Traditional kava kava drinks are prepared differently, after grinding the roots by chewing and spitting them out. Needless to say, this not an option for commercial preparations. The studies that point to liver toxicity after kava kava intake included patients with a history of alcohol consumption. In other cases, kava kava was taken with other prescribed drugs, so the specific contribution of kava kava to the damage is unclear [ 21 , 22 ]. Since the early s, 11 cases of kava kava-related liver injuries have been reported, four of which resulted in death. As a result, kava kava was banned in Canada and a number of European countries [ 23 ]. There was one case of acute hepatitis associated with kava-kava in a year-old girl. She recovered after a liver transplant [ 24 ]. But until more studies are out, people with liver problems are better off avoiding it. According to another study, red clover might interact with non-steroidal anti-inflammatory drugs, particularly aspirin, and cause adverse reactions. Such adverse events are common in herbal supplements that contain coumarin [ 26 ]. Liver toxicity caused by greater celandine Chelidonium majus was reported in 16 patients [ 27 , 28 ]. One person developed acute hepatitis after consuming an herbal preparation of this plant [ 29 ]. Surprisingly, greater celandine protected mice and rats from liver damage in several studies [ 30 , 31 , 32 , 33 ]. Germander Teucrium chamaedrys may cause hepatitis and even liver cirrhosis, as has been reported in some case studies [ 34 , 35 , 36 , 37 , 38 , 39 ]. In , germander powder-containing capsules were banned from the French market after an epidemic of 30 cases of hepatitis [ 20 ]. Sassafras Sassafras albidum oil has been classified as a liver carcinogen of low grade due to its main component safrole. A derivative of this compound also caused liver toxicity in mice [ 24 , 40 ]. Usnic acid can induce oxidative stress and inhibit mitochondrial function in liver cells, which may contribute to its hepatotoxicity [ 43 , 44 ]. It caused various levels of damage, potentially leading to liver failure in several cases. The effects were possibly due to its pyrrolizidine alkaloids [ 45 , 46 , 47 ]. Liver injury associated with oral administration of Aloe vera was first reported in The injury, which occurs in rare cases only, typically arises between 3 and 24 weeks of starting oral aloe [ 48 ]. According to one report, three women aged 55, 57 and 65 suffered acute hepatitis after taking aloe preparations for months. Liver enzymes returned to normal upon discontinuation of the oral aloe preparations [ 49 ]. In 2 other cases, two women 27 and 73 years old were admitted to the hospital for acute hepatitis after taking aloe vera preparations for several weeks [ 50 , 51 ]. Mistletoe Viscum album has been reported to cause liver injury increased levels of the markers AST and ALT and hepatitis in several people [ 52 , 53 , 54 ]. In South Africa, impila Callilepis laureola has been associated with some cases of hepatitis and kidney damage. In one case, a mother who consumed impila died of liver necrosis. Valerian is usually safe when taken at typical doses for weeks.
Dietary Coleus forskohlii extract generates dose-related hepatotoxicity in mice	Figure 2. Functioh, L. Year of publication:. Article ADS CAS PubMed PubMed Central Google Scholar Rebelo, S. Not many studies speak to its liver-damaging effects.

SelfHacked has livwr Meal planning for diabetics sourcing guidelines in livef health industry and ane almost exclusively link to medically peer-reviewed studies, liber on PubMed. We believe Pycnogenol and wound healing the most accurate liveg is found directly in adn scientific source. We are dedicated Functkon providing the most scientifically valid, unbiased, and comprehensive Immune health remedies on any given topic. Our team comprises of trained MDs, PhDs, pharmacists, qualified scientists, and certified health and wellness specialists. Our science team is put through the strictest vetting process in the health industry and we often reject applicants who have written articles for many of the largest health websites that are deemed trustworthy. Our science team must pass long technical science tests, difficult logical reasoning and reading comprehension tests. They are continually monitored by our internal peer-review process and if we see anyone making material science errors, we don't let them write for us again.