Histological patterns in drug-induced liver disease.

J Clin Pathol. 2009 Jun; 62(6): 481-92Ramachandran R, Kakar SThe diagnosis of drug-induced liver injury (DILI) is a challenging problem, often confounded by incomplete clinical information and the difficulty of eliciting exposure to herbal products, over-the-counter agents and toxins. The task is further rendered difficult on biopsy, as drugs can mimic all the patterns found in primary liver disease. Acute hepatitis, with or without cholestasis, is the most common histological pattern of DILI, and drugs such as acetaminophen are the leading causes of acute liver failure. Most cases of DILI resolve on discontinuation of the drug, but recovery can take months or rarely the disease can progress despite drug withdrawal. Drugs such as methotrexate can lead to chronic hepatitis and cirrhosis, while others such as minocycline, nitrofurantoin and methyldopa are implicated in autoimmune hepatitis. Prolonged cholestasis and ductopenia resembling primary chronic biliary disease can occur. Drug-induced steatohepatitis is also an uncommon pattern, but is well described with drugs such as amiodarone and irinotecan. In the presence of risk factors such as obesity and diabetes, some drugs such as tamoxifen, oestrogens and nifedipine can precipitate or exacerbate steatohepatitis. Other observed patterns include granulomatous hepatitis, vascular injury (eg, sinusoidal obstruction syndrome), Ito cell lipidosis and neoplasms (eg, adenomas).

In vitro anti-fibrotic activities of herbal compounds and herbs.

Nephrol Dial Transplant. 2009 May 27; Hu Q, Noor M, Wong YF, Hylands PJ, Simmonds MS, Xu Q, Jiang D, Hendry BM, Xu QBACKGROUND: We recently developed high-throughput assays of inflammation-independent anti-fibrotic activities based on TGF-beta1-induced total collagen accumulation and nodule formation in normal rat kidney fibroblasts. METHODS: These assays were applied to examine the anti-fibrotic activities of 21 compounds isolated from plants used in Chinese medicine and methanol extracts of 12 Chinese herbs. Lactate dehydrogenase release assay and cell detachment index were used to monitor cytotoxicity. Changes in fibrogenic molecular markers were observed by reverse transcriptase quantitative polymerase chain reaction and high-content imaging analysis of immunofluorescence. RESULTS: Three flavonoids (quercetin, baicalein and baicalin) and two non-flavonoids (salvianolic acid B and emodin) demonstrated anti-fibrotic activities in both total collagen accumulation and nodule formation assays. The remaining 16 compounds had little anti-fibrotic effect or were cytotoxic. The anti-fibrotic compounds suppressed collagen I expression at both mRNA and protein levels and also variably suppressed alpha-smooth muscle actin expression and bromodeoxyuridine incorporation. Methanol extracts of Scutellaria baicalensis Georgi, Salvia miltiorrhiza Bunge and Rheum palmatum L., which are rich sources of baicalein, baicalin, salvianolic acid B and emodin, respectively, also showed in vitro anti-fibrotic activities. CONCLUSIONS: Five herbal compounds and three herbal extracts have in vitro anti-fibrotic activities. These data warrant further studies on these anti-fibrotic entities and suggest it a promising strategy to discover new anti-fibrotic drugs by screening more plant materials.

Hypoglycemic effect of quassinoids from Brucea javanica (L.) Merr (Simaroubaceae) seeds.

J Ethnopharmacol. 2009 May 8; Noorshahida A, Wong TW, Choo CYETHNOPHARMACOLOGICAL RELEVANCE: The seeds of Brucea javanica (L.) Merr (Simaroubaceae) are recommended by traditional practitioners for the treatment of diabetes mellitus. Aim of the Study: To identify the compounds responsible for blood glucose lowering effect and evaluate the acute toxicity of the compounds. MATERIALS AND METHODS: Extracts, fractions and subfractions were administered to normoglycemic mice and the blood glucose concentration was monitored for 8h. Bioactive compounds isolated through column chromatography were administered to normoglycemic mice and streptozotocin (STZ) rats with monitoring of blood glucose concentration at 0-8h. The acute toxicity was evaluated in mice. RESULTS: Bioactivity guided fractionation led to the isolation of bruceines E (1) and D (2). Normoglycemic mice administered with 1mg/kg of 1 and 2 exhibited significant blood glucose concentration reduction of 40.07+/-11.45% and 48.82+/-13.34 %, respectively. STZ induced diabetic rats administered with 1 and 2 exhibited significant blood glucose concentration reduction of 73.57+/-13.64% and 87.99+/-2.91%, respectively. CONCLUSION: The reduction of blood glucose concentration by both bruceines were comparable to glibenclamide and they might act as an insulin secretagogue. The presence of a hydroxyl moiety at C(2) in 1 reduced the toxic effect by nine fold compared to 2.

Herbal Medicines in the Management of Urolithiasis: Alternative or Complementary?

Planta Med. 2009 May 14; Butterweck V, Khan SRKidney stone formation or urolithiasis is a complex process that results from a succession of several physicochemical events including supersaturation, nucleation, growth, aggregation, and retention within the kidneys. Epidemiological data have shown that calcium oxalate is the predominant mineral in a majority of kidney stones. Among the treatments used are extracorporeal shock wave lithotripsy (ESWL) and drug treatment. Even improved and besides the high cost that imposes, compelling data now suggest that exposure to shock waves in therapeutic doses may cause acute renal injury, decrease in renal function and an increase in stone recurrence. In addition, persistent residual stone fragments and the possibility of infection after ESWL represent a serious problem in the treatment of stones. Furthermore, in spite of substantial progress in the study of the biological and physical manifestations of kidney stones, there is no satisfactory drug to use in clinical therapy. Data from IN VITRO, IN VIVO and clinical trials reveal that phytotherapeutic agents could be useful as either an alternative or an adjunctive therapy in the management of urolithiasis. The present review therefore critically evaluates the potential usefulness of herbal medicines in the management of urolithiasis.