Protective effect of Pisonia aculeata on Rifampicin and Isoniazid induced hepatotoxicity in rats

Pisonia aculeata is traditionally used in treatment of liver disorder and thought to have a protective effect which may be beneficial to reduce symptoms of hepatotoxicity. The current study aimed to evaluate the scientific merit of these anecdotal claims in an in vivo model. Methanolic extract of leaves of Pisonia aculeata (250 and 500 mg/kg, p.o.) showed a remarkable hepatoprotective and antioxidant activity against　 Rifampicin and Isoniazid induced hepatotoxicity as judged from the serum marker enzymes and　antioxidant levels in liver tissues. Acetaminophen induced a significant rise in aspartate　amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP),　total bilirubin, gamma glutamate transpeptidase (GGTP), lipid peroxidase (LPO) with a reduction of total protein, superoxide dismutase (SOD), catalase, glutathione peroxidase　(GPx), reduced glutathione (GSH), Glutathione reductase (GR), Vitamin C and E. Treatment of rats with different doses of　plant extract (200 and 300 mg/kg) significantly (P<0.001) altered serum marker　enzymes and antioxidant levels to near normal against acetaminophen treated rats. Also the extract was effectively altered the drug metabolizing enzymes such as Cytochrome P450, NADPH   Cytochrome C reductase and glutathione S transferase. The activity of the extract at dose of 500 mg/kg was comparable to the standard drug, silymarin (50 mg/kg, p.o.). Histopathological changes of liver sample were compared with respective control. Results indicate the hepatoprotective and antioxidant properties of Pisonia aculeata against rifampicin and isoniazid -induced hepatotoxicity in rats. Keywords: Pisonia aculeata; Rifampicin; Isoniazid; Biochemical parameters;　Antioxidants; Lipid peroxidation; Histopathology

Antimetastatic Effects of Phyllanthus on Human Lung (A549) and Breast (MCF-7) Cancer Cell Lines

BACKGROUND: Current chemotherapeutic drugs kill cancer cells mainly by inducing apoptosis. However, they become ineffective once cancer cell has the ability to metastasize, hence the poor prognosis and high mortality rate. Therefore, the purpose of this study was to evaluate the antimetastatic potential of Phyllanthus (P. niruri, P. urinaria, P. watsonii, and P. amarus) on lung and breast carcinoma cells. METHODOLOGY/PRINCIPAL FINDINGS: Cytotoxicity of Phyllanthus plant extracts were first screened using the MTS reduction assay. They were shown to inhibit MCF-7 (breast carcinoma) and A549 (lung carcinoma) cells growth with IC(50) values ranging from 50-180 µg/ml and 65-470 µg/ml for methanolic and aqueous extracts respectively. In comparison, they have lower toxicity on normal cells with the cell viability percentage remaining above 50% when treated up to 1000 µg/ml for both extracts. After determining the non-toxic effective dose, several antimetastasis assays were carried out and Phyllanthus extracts were shown to effectively reduce invasion, migration, and adhesion of both MCF-7 and A549 cells in a dose-dependent manner, at concentrations ranging from 20-200 µg/ml for methanolic extracts and 50-500 µg/ml for aqueous extracts. This was followed by an evaluation of the possible modes of cell death that occurred along with the antimetastatic activity. Phyllanthus was shown to be capable of inducing apoptosis in conjunction with its antimetastastic action, with more than three fold increase of caspases-3 and -7, the presence of DNA-fragmentation and TUNEL-positive cells. The ability of Phyllanthus to exert antimetastatic activities is mostly associated to the presence of polyphenol compounds in its extracts. CONCLUSIONS/SIGNIFICANCE: The presence of polyphenol compounds in the Phyllanthus plant is critically important in the inhibition of the invasion, migration, and adhesion of cancer cells, along with the involvement of apoptosis induction. Hence, Phyllanthus could be a valuable candidate in the treatment of metastatic cancers

Growth Inhibition of Human Gynecologic and Colon Cancer Cells by Phyllanthus watsonii through Apoptosis Induction

Phyllanthus watsonii Airy Shaw is an endemic plant found in Peninsular Malaysia. Although there are numerous reports on the anti cancer properties of other Phyllanthus species, published information on the cytotoxicity of P. watsonii are very limited. The present study was carried out with bioassay-guided fractionation approach to evaluate the cytotoxicity and apoptosis induction capability of the P. watsonii extracts and fractions on human gynecologic (SKOV-3 and Ca Ski) and colon (HT-29) cancer cells. P. watsonii extracts exhibited strong cytotoxicity on all the cancer cells studied with IC50 values of ≤ 20.0 µg/mL. Hexane extract of P. watsonii was further subjected to bioassay-guided fractionation and yielded 10 fractions (PW-1→PW-10). PW-4→PW-8 portrayed stronger cytotoxic activity and was further subjected to bioassay-guided fractionation and resulted with 8 sub-fractions (PPWH-1→PPWH-8). PPWH-7 possessed greatest cytotoxicity (IC50 values ranged from 0.66 – 0.83 µg/mL) and was selective on the cancer cells studied. LC-MS/MS analysis of PPWH-7 revealed the presence of ellagic acid, geranic acid, glochidone, betulin, phyllanthin and sterol glucoside. Marked morphological changes, ladder-like appearance of DNA and increment in caspase-3 activity indicating apoptosis were clearly observed in both human gynecologic and colon cancer cells treated with P. watsonii especially with PPWH-7. The study also indicated that P. watsonii extracts arrested cell cycle at different growth phases in SKOV-3, Ca Ski and HT-29 cells. Cytotoxic and apoptotic potential of the endemic P. watsonii was investigated for the first time by bioassay-guided approach. These results demonstrated that P. watsonii selectively inhibits the growth of SKOV-3, Ca Ski and HT-29 cells through apoptosis induction and cell cycle modulation. Hence, P. watsonii has the potential to be further exploited for the discovery and development of new anti cancer drugs

In vitro permeation studies of diclofenac diethylamine from newly developed oleogel bases

The study was designed to investigate the feasibility of developing a transdermal drug dosage form of diclofenac diethylamine (DDA). The in vitro release and diffusion characteristics of  DDA from two dermatological oleogel bases were studied using full thickness skin from the abdominal hairless surface of rabbit, as the diffusion barriers. The bases included, sesame oil with colloidal silicon dioxide (CSD-SO) oleogel and light liquid paraffin with colloidal silicon dioxide (CSD-LP) oleogel both containing 1.16 % w/w DDA. Results of the diffusion studies show that the CSD-SO oleogel exhibited the optimum drug release. The data also revealed that CSD-SO oleogel gave higher diffusion and permeability coefficient values when compared to (CSD-LP) oleogel and these results correlated well with those of drug release.Keywords: Diclofenac diethylamine , skin permeability, oleogels, drug release, transdermalJournal of Pharmaceutical and Allied Sciences, Vol. 7 No. 3 (2010

Short Communication: Improved Stability and Efficacy of Diclofenac Diethylamine In an Oleogel Based Formulation

An oleogel-based formulation of diclofenac diethylamine (DFDA) was prepared and evaluated for enhanced stability and efficacy. Efficacy was evaluated by carrageenan-induced paw oedema method on albino rats and compared with marketed emulgels. The present findings revealed that the developed oleogel formulation of DFDA is more stable and effective than the marketed product. Enhanced efficacy of the formulation is probably due to its increased sustainability and penetrability into the skin in oleogel base

Research Paper - Antitumor activity of Indigofera aspalathoides on Ehrlich ascites carcinoma in mice

Objective: To evaluate the antitumor activity of the ethanol extract of Indigofera aspalathoides (EIA) in mice. Material and Methods: The antitumor activity of EIA was evaluated against the Ehrlich ascites carcinoma (EAC) tumor model. The activity was assessed using survival time, peritoneal cell count, hematological studies, solid tumor mass and in vitro cytotoxicity. Results: Oral administration of EIA increased the survival time and normal peritoneal cell count. Hematological parameters, protein and PCV, which were altered by tumor inoculation, were restored. Solid tumor mass was also significantly reduced. EIA was found to be cytotoxic in the in vitro model. Conclusion: EIA possesses significant antitumor activity