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Herbal Supplements and Health
Published in Anil K. Sharma, Raj K. Keservani, Surya Prakash Gautam, Herbal Product Development, 2020
Himangini Bansal, Sakshi Bajaj
A few people use germander as a mouthwash to refresh the breath and eliminate germs in the mouth. In production, germander is utilized as a flavoring agent in alcoholic drinks. Germander (Teucrium chamaedrys) is a sweet-smelling plant inside the “mint family” belonging to genus Teucrium. Its blooms are utilized as a traditional drug to treat diabetes, dyspepsia, and gout. However, constant utilization of germander results in hepatotoxicity. In fact, the toxic results of germander are first visible inside 9 weeks of use and are manifested by way of jaundice and accelerated liver enzymes (ALT and AST). After cessation of the drug, restoration may take 6 weeks to half a year. The mechanism of toxicity is believed to be identified with the diterpenoid component present in plants that are converted into stronger toxins inside the liver. The main hepatotoxic diterpene present in germander is teucrin A, that is, bioactivated through the cytochrome P450 enzymes within the liver. Another hepatotoxic element of germander is teuchmaedryn A (Dasgupta and Sepulveda, 2013; Mattéi et al., 1995; Polymeros et al., 2002).
Ethnobotany of Teucrium Species
Published in José L. Martinez, Amner Muñoz-Acevedo, Mahendra Rai, Ethnobotany, 2019
Milan S. Stanković, Nenad M. Zlatić
The species Teucrium chamaedrys mostly grows in arid rocky localities of calcareous origin. Rarely can it be found on serpentine and silicate substrate. The species may inhabit areas whose altitudes range from 200 to 1500 m (Horvat et al. 1974, Diklic 1974). It is widely distributed in deciduous, mixed, and coniferous forests as well as in communities of broadleaved evergreen and deciduous forests of bushy vegetation. Meadows, pastures, continental steppes and sands are also frequent habitats of Teucrium chamaedrys (Horvat et al. 1974, Diklic 1974, Ellenberg and Strutt 2009).
France
Published in Rowena K. Richter, Herbal Medicine, 2013
In 1992, herbal tea capsules that contained Teucrium chamaedrys (germandrée petit-chêne) were implicated in twenty-six reports of cytolitic hepatitis. Six herbal products were recalled a…esult. They had been approved through an abridged procedure based on the positive list.
Bioactivation of herbal constituents: mechanisms and toxicological relevance
Published in Drug Metabolism Reviews, 2019
Germander (Teucrium chamaedrys L.), a furano diterpenoid-containing herbal plant, has been used as a folk medicine for several purposes, ranging from the treatment of rheumatism to use as a diuretic and antiseptic agent (Delaveau 1986). In the early 1990s, promotion of slimming capsules containing germander powder as an adjuvant to weight control diets led to an epidemic of liver injury with over 30 cases of cytolytic hepatitis in France, including several fatalities due to fulminant hepatic necrosis (Larrey et al. 1992; Mostefa-Kara et al. 1992). Many cases showed signs of immunoallergic type of hepatitis since a rechallenge caused early recurrence of the toxicity. Germander-derived human liver injury was replicated in mice and shown to be attributed to its furan-containing neoclerodane diterpenoids such as teucrin A and teuchamaedryn A (Kouzi et al. 1994; Loeper et al. 1994). Oral administration of teucrin A, a major constituent of furano diterpenoids in germander, produced the same midzonal hepatic necrosis in mice as extracts enriched in these compounds (Kouzi et al. 1994). Germander- or teucrin A-induced hepatotoxicity was accompanied by depletion of intracellular GSH and alkylation of protein thiols, and GSH depletion enhanced the hepatotoxic effects of both teucrin A and teucrin A-containing extracts (Lekehal et al. 1996). The hepatotoxicity was enhanced by CYP3A inducers and blocked by CYP3A inhibitors, supporting CYP3A-mediated bioactivation of teucrin A and formation of reactive species capable of covalently alkylating protein nucleophiles (Kouzi et al. 1994; Lekehal et al. 1996)
How can we improve the safe use of herbal medicine and other natural products? A clinical pharmacologist mission
Published in Expert Review of Clinical Pharmacology, 2020
Elena Y. Enioutina, Kathleen M. Job, Lubov V. Krepkova, Michael D. Reed, Catherine M. Sherwin
Consumers generally consider marketed DSs as a safe alternative to conventional medications and often believe they can consume as much as they want. However, the use of DSs, especially in excessive amounts, can lead to multiple untoward effects, including severe adverse reactions and toxicity. The most common involve allergic reactions and hepatotoxicity [29–32]. Bunchorntavakul and Reddy reviewed nine studies conducted between 2000 and 2008 and identified that 2–73% of hepatotoxicity cases were associated with the use of medicinal herbs and DSs [31]. More recent studies from the Drug-Induced Liver Injury Network (DILIN) demonstrated that the percentage of NP/DS associated liver injuries has increased from 7% in 2004–2005 to 20% in 2013–2014 [33]. According to this study, many cases of hepatotoxicity were associated with the use of multicomponent DSs [33]. Teschke and Eickhoff report the mechanisms of hepatic injury that are primarily dose-independent idiosyncratic, unpredictable, dose-independent, immunologically or metabolically driven, or intrinsic, a predictable and dose-dependent injury [34]. Clinical presentations of herb-associated liver injury range from asymptomatic elevation of liver enzymes in the blood (i.e. alanine transaminase, aspartate transaminase, gamma-glutamyl transpeptidase) to cholestasis and even acute liver failure resulting in liver transplant. R-value is a significant factor in determining the degree and pattern of hepatic injury [30]. This value is defined as alanine aminotransferase (ALT)/upper limit of normal levels of ALT divided by alkaline phosphatase (APT)/upper limit of normal APT. R-value ≥5 suggests hepatocellular, < 2 cholestatic, and between 2 and 5 mixed patterns of liver injury. Stournaras and Tziomalos suggest that many herbal preparations induce hepatocellular liver injury [30]. The use of bodybuilding supplements has been associated with cholestasis, while the use of high doses of green tea extracts can result in hepatic injury [30,33]. Germanders (Teucrium chamaedrys L.), Greater celandine (Chelidonium majus L.), Babchi (Psoralea corylifolia L., Boh-Gol-Zhee) Comfrey (Symphytum officinale L.), Chaparral (Larrea tridentate (DC.) Coville), Black Cohosh (Cimicifuga racemose) are examples of medicinal herbs with known hepatotoxic properties [30–32]. Recent case reports suggest that concomitant use of excessive amounts of MHs (e.g. ginger and Eleuthero) may potentiate conventional drug hepatotoxicity [35,36].