Coffee and liver diseases.

Effects of low-dose liquorice alone or in combination with hydrochlorothiazide on the plasma potassium in healthy volunteers.

Effects of Withania somnifera (Ashwagandha) and Terminalia arjuna (Arjuna) on physical performance and cardiorespiratory endurance in healthy young adults.

Inhibitory effect of methanol extract of Ganoderma lucidum on acute itch-associated responses in mice.

Selective inhibition of the tumor marker AKR1B10 by antiinflammatory N-phenylanthranilic acids and glycyrrhetic acid.

Schisandrin B-induced glutathione antioxidant response and cardioprotection are mediated by reactive oxidant species production in rat hearts.

Coffee and liver diseases.

Fitoterapia. 2010 Jul;81(5):297-305

Authors: Muriel P, Arauz J

Coffee consumption is worldwide spread with few side effects. Interestingly, coffee intake has been inversely related to the serum enzyme activities gamma-glutamyltransferase, and alanine aminotransferase in studies performed in various countries. In addition, epidemiological results, taken together, indicate that coffee consumption is inversely related with hepatic cirrhosis; however, they cannot demonstrate a causative role of coffee with prevention of liver injury. Animal models and cell culture studies indicate that kahweol, diterpenes and cafestol (some coffee compounds) can function as blocking agents by modulating multiple enzymes involved in carcinogenic detoxification; these molecules also alter the xenotoxic metabolism by inducing the enzymes glutathione-S-transferase and inhibiting N-acetyltransferase. Drinking coffee has been associated with reduced risk of hepatic injury and cirrhosis, a major pathogenic step in the process of hepatocarcinogenesis, thus, the benefit that produces coffee consumption on hepatic cancer may be attributed to its inverse relation with cirrhosis, although allowance for clinical history of cirrhosis did not completely account for the inverse association. Therefore, it seems to be a continuum of the beneficial effect of coffee consumption on liver enzymes, cirrhosis and hepatocellular carcinoma. At present, it seems reasonable to propose experiments with animal models of liver damage and to test the effect of coffee, and/or isolated compounds of this beverage, not only to evaluate the possible causative role of coffee but also its action mechanism. Clinical prospective double blind studies are also needed.

PMID: 19825397 [PubMed - indexed for MEDLINE]

Effects of low-dose liquorice alone or in combination with hydrochlorothiazide on the plasma potassium in healthy volunteers.

Blood Press. 2009 Sep;18(4):192-5

Authors: Hukkanen J, Ukkola O, Savolainen MJ

Both liquorice and thiazide diuretics have hypokalaemic effects. In spite of their prevalent use, there are no studies on hypokalaemia caused by the combination of liquorice and thiazides. We recruited 10 healthy volunteers in order to study the effects of 32 g liquorice alone or in combination with 25mg hydrochlorothiazide a day for 2 weeks. The trial had a randomized, open and crossover design. During the liquorice phase, there were no changes in plasma potassium, sodium, creatinine, renin activity, serum aldosterone, blood pressure or heart rate. Weight tended to increase by 0.4 kg (70.2 to 70.6 kg; p=0.056). During the liquorice-hydrochlorothiazide phase, the plasma potassium decreased by 0.32 mmol/l (p=0.0015), plasma renin activity increased by 1.6 microg/l/h (p=0.0064) and the weight decreased by 0.9 kg (70.5 to 69.6 kg, p=0.0065). Twenty per cent of the subjects (2/10) became hypokalaemic during the combined liquorice-hydrochlorothiazide treatment. Furthermore, both subjects developed hypokalaemia within the first week of the combined treatment leading to premature discontinuation. The evaluation of liquorice consumption habits is warranted when initiating thiazide medications to avoid the excessive risk of hypokalaemia associated with the combined use of low-dose liquorice and thiazide diuretics.

PMID: 19562574 [PubMed - indexed for MEDLINE]

Effects of Withania somnifera (Ashwagandha) and Terminalia arjuna (Arjuna) on physical performance and cardiorespiratory endurance in healthy young adults.

Int J Ayurveda Res. 2010 Jul;1(3):144-9

Authors: Sandhu JS, Shah B, Shenoy S, Chauhan S, Lavekar GS, Padhi MM

Several medicinal plants have been described to be beneficial for cardiac ailments in Ayurveda like Ashwagandha and Arjuna. Ashwagandha-categorised as Rasayanas, and described to promote health and longevity and Arjuna primarily for heart ailments. coronary artery disease, heart failure, hypercholesterolemia, anginal pain and can be considered as a useful drug for coronary artery disease, hypertension and ischemic cardiomyopathy.

PMID: 21170205 [PubMed - in process]

Inhibitory effect of methanol extract of Ganoderma lucidum on acute itch-associated responses in mice.

Biol Pharm Bull. 2010;33(5):909-11

Authors: Zhang Q, Andoh T, Konno M, Lee JB, Hattori M, Kuraishi Y

In this study, the antipruritic effect of the methanol extract of Ganoderma lucidum (MEGL) was studied in mice. Oral administration of MEGL (10-1000 mg/kg) produced a dose-dependent inhibition of scratching, an itch-related response, induced by intradermal 5-hydroxytryptamine (5-HT) (100 nmol/site), alpha-methyl-5-HT (100 nmol/site), and proteinase-activated receptor-2 (PAR(2))-activating peptide SLIGRL-NH(2) (50 nmol/site). However, MEGL (100-1000 mg/kg) did not inhibit the scratching induced by histamine (100 nmol/site), substance P (100 nmol/site), and compound 48/80 (10 microg/site). These results raise the possibility that MEGL is effective against pruritus mediated by proteinases and 5-HT and that primary afferents expressing PAR(2) and 5-HT(2A) receptors are the sites of its action.

PMID: 20460776 [PubMed - indexed for MEDLINE]

Selective inhibition of the tumor marker AKR1B10 by antiinflammatory N-phenylanthranilic acids and glycyrrhetic acid.

Biol Pharm Bull. 2010;33(5):886-90

Authors: Endo S, Matsunaga T, Soda M, Tajima K, Zhao HT, El-Kabbani O, Hara A

A human aldose reductase-like protein, AKR1B10 in the aldo-keto reductase (AKR) superfamily, was recently identified as a tumor marker of several types of cancer. Tolrestat, an aldose reductase inhibitor (ARI), is known to be the most potent inhibitor of the enzyme. In this study, we compared the inhibitory effects of other ARIs including flavonoids on AKR1B10 and aldose reductase to evaluate their specificity. However, ARIs showed lower inhibitory potency for AKR1B10 than for aldose reductase. In the search for potent and selective inhibitors of AKR1B10 from other drugs used clinically, we found that non-steroidal antiinflammatory N-phenylanthranilic acids, diclofenac and glycyrrhetic acid competitively inhibited AKR1B10, showing K(i) values of 0.35-2.9 microM and high selectivity to this enzyme (43-57 fold versus aldose reductase). Molecular docking studies of mefenamic acid and glycyrrhetic acid in the AKR1B10-nicotinamide adenine dinucleotide phosphate (NADP(+)) complex and site-directed mutagenesis of the putative binding residues suggest that the side chain of Val301 and a hydrogen-bonding network among residues Val301, Gln114 and Ser304 are important for determining the inhibitory potency and selectivity of the non-steroidal antiinflammatory drugs. Thus, the potent and selective inhibition may be related to the cancer chemopreventive roles of the drugs, and their structural features may facilitate the design of new anti-cancer agents targeting AKR1B10.

PMID: 20460771 [PubMed - indexed for MEDLINE]

Schisandrin B-induced glutathione antioxidant response and cardioprotection are mediated by reactive oxidant species production in rat hearts.

Biol Pharm Bull. 2010;33(5):825-9

Authors: Chen N, Ko M

To investigate the involvement of reactive oxidant species (ROS), presumably arising from cytochrome P-450 (CYP)-catalyzed metabolism of schisandrin B (Sch B), in triggering glutathione antioxidant response, Sch B induced reduced nicotinamide adenine dinucleotide phosphate (NADPH)-dependent and CYP-catalyzed reaction and associated ROS production were examined in rat heart microsomes. Sch B analogs were also studied for comparison. Using rat heart microsomes as a source of CYP, Sch B and schisandrin C (Sch C), but not schisandrin A and dimethyl diphenyl bicarboxylate (an intermediate compound derived from the synthesis of Sch C), were found to serve as co-substrate for the CYP-catalyzed NADPH oxidation reaction, with concomitant production of ROS. The stimulation of CYP-catalyzed NADPH oxidation reaction and/or ROS production by Sch B or Sch C correlated with the increase in mitochondrial reduced glutathione level and protection against ischemia/reperfusion (I/R) injury in rat hearts. The involvement of ROS in Sch B-induced cardioprotection was further confirmed by the suppressive effect produced by N-acetylcysteine or alpha-tocopherol pretreatment. Taken together, these results suggest that Sch B-induced glutathione antioxidant response and cardioprotection may be mediated by ROS arising from CYP-catalyzed reaction.

PMID: 20460761 [PubMed - indexed for MEDLINE]