Uzma Saleem

Inhibitors of Apoptotic Proteins: New Targets for Anticancer Therapy

Inhibitors of apoptotic proteins (IAPs) can play an important role in inhibiting apoptosis by exerting their negative action on caspases (apoptotic proteins). There are eight proteins in this family: NAIP/BIRC1/NLRB, cellular IAP1 (cIAP1)/human IAP2/BIRC2, cellular IAP2 (cIAP2)/human IAP1/BIRC3, X‐linked IAP (XIAP)/BIRC4, survivin/BIRC5, baculoviral IAP repeat (BIR)‐containing ubiquitin‐conjugating enzyme/apollon/BIRC6, livin/melanoma‐IAP (ML‐IAP)/BIRC7/KIAP, and testis‐specific IAP (Ts‐IAP)/hILP‐2/BIRC8. Deregulation of these inhibitors of apoptotic proteins (IAPs) may push cell toward cancer and neurodegenerative disorders. Inhibitors of apoptotic proteins (IAPs) may provide new target for anticancer therapy. Drugs may be developed that are inhibiting these IAPs to induce apoptosis in cancerous cells.

Investigation of in vivo antioxidant activity of Euphorbia helioscopia latex and leaves methanol extract: a target against oxidative stress induced toxicity

OBJECTIVE To evaluate in vivo antioxidant activity of latex and leaves methanol extract of Euphorbia helioscopia using mice as experimental animals. METHODS The plant was collected, identified, dried under shade, ground to fine powder and extraction was done. Latex was collected in dried bottles by cutting the stem. Oxidative stress was induced in mice with acute toxic dose of paracetamol administered intrperitoneally. Latex and leaves methanol extract (600 and 1 200 mg/kg) orally, once a day, were given to mice for two weeks. Then oxidative stress biomarkers were measured in tissue homogenates and serum. RESULTS Leaves methanol extract exhibited prominent in vivo antioxidant effect as compared to latex. Results showed significant rise in antioxidant enzymes (catalase, superoxide dismutase and glutathione) levels at 1 200 mg/kg dose of extract. Thus, extract helped to detoxify the free radicles by increasing antioxidant enzymes levels. Malondialdehyde value decreased significantly with extract (1 200 mg/kg) which was indicator of extracts power to inhibit the generation of free radicals. Extract (1 200 mg/kg) exhibited maximum cure against stress induced changes in liver, kidney, lipid profile parameters and complete blood count. CONCLUSIONS Leaves methanol extract of Euphorbia helioscopia raised antioxidant enzymes levels in mice. It showed hepatorenal-curative effect, hypolipidemic effect and hemostasis potential. Thus, it can help the biological systems to fight against stress induced pathological conditions.

THERAPEUTIC EFFICACY AND PHARMACOECONOMICS EVAULATION OF PAMIDRONATE VERSUS ZOLEDRONIC ACID IN MULTIPLE MYELOMA PATIENTS

Sixty patients of multiple myeloma were randomized into two equal groups to receive Pamidronate and Zoledronic acid intravenously every month for a total of six months. The primary endpoint was to compare the therapeutic efficacy of both drugs by the resolution of hypercalcemia, prevention of skeletal related events and pathological fractures. The secondary endpoints were to assess patient compliance on the basis of quality of life score before and after treatment with Pamidronate and Zoledronic acid and to analyze the cost effectiveness of both drugs., Pamidronate was found to be more effective in the resolution of hypercalcemia as compared to Zoledronic acid, whereas Zoledronic acid reduced the overall proportion of skeletal related events (45.9%) in comparison with Pamidronate (54.1%). Overall Quality of life scores were not significantly influenced by either the response or the occurrence of adverse event but were statistically significant (P=0.000), with in the treatment groups. Patients on Zoledronic acid were more comfortable due to short administration time of l5minutes as compared to 2 hours of Pamidronate. The average cost of six months’ treatment with Zoledronic acid was significantly higher (PKR=90, 000 or USD 1,052) in comparison with Pamidronate (PKR=39, 000 USD 456. Zoledronic acid reduced the risk of developing skeletal complications including hypercalcemia and was significantly more effective in reducing the incidence of hypocalcemia. The incidence of renal impairment among patients treated with Zoledronic acid was significantly higher, but severity of nephrotoxicity was more with Pamidronate. The most common adverse effects were pain, vomiting and fatigue in both treatment groups. Comparatively, Pamidronate was more effective in resolution of hypercalcemia, while Zoledronic acid have better therapeutic effects in reduction of skeletal related events and pathological fractures.

Is folklore use of Euphorbia helioscopia devoid of toxic effects

Abstract Objective: To evaluate acute toxic effects of Euphorbia helioscopia in order to assure the safety and usefulness of herbal remedy. Materials and methods: The Organization for Economic Cooperation and Development (OECD) for chemical testing guidelines No. 425 for acute oral toxicity testing were followed in this study. Mice were divided into three groups (n = 5). Group I served as control. Groups II and III were administered methanol extract of E. helioscopia leaves and latex orally at dose of 2000 mg/kg, respectively. Then, all the animals were observed for two weeks. Blood sampling was done by cardiac puncture after 14 days from each group for biochemical analysis. Histopathology was performed to find out any microscopic lesion in vital organs. Results and discussion: LD50 was found greater than 2000 mg/kg. There was decrease in cholesterol, triglycerides, LDL and VLDL levels of latex and leaves with methanol extract-treated animals, with respect to control indicating plant’s hypolipidemic effect. On macroscopic examination, no lesions were found on vital organs, such as liver, heart and kidney; and normal architecture was observed on microscopic examination. Conclusion: On the basis of results, it was concluded that methanol extract of E. helioscopia leaves and latex were devoid of toxic effects in acute toxicity study.

Anti-nociceptive, anti-inflammatory and anti-pyretic activities of latex and leaves methanol extract of Euphorbia helioscopia

Abstract Objective To evaluate anti-nociceptive, anti-inflammatory and anti-pyretic activities of latex and leaves methanol extract of Euphorbia helioscopia against chemical (acetic acid induced writhing and formalin tests) and thermal pain stimuli (hot plate test), carrageenan induced paw edema and brewers yeast induced pyrexia in mice respectively. Methods Pain, inflammation and pyrexia were induced in mice. Leaves methanol extract and latex were administered to mice, orally at doses, 100, 200 and 300 mg/kg. Results Leaves methanol extract at all used doses had 100% pain protection against peripherally induced pain pathway (investigated by acetic acid induced writhing test and late phase of formalin test). While central anti-nociceptive effect (measured by hot plate test and early phase of formalin test) was found dose dependent with extract and latex. Similarly a dose dependent trend was observed in anti-inflammatory and anti-pyretic effects and leaves methanol extract showed maximal anti-inflammatory (81.25%) and anti-pyretic (45.36%) effects at 300 mg/kg dose. Conclusions From the data obtained, it can be concluded that Euphorbia helioscopia possesses marked anti-nociceptive, anti-inflammatory and anti-pyretic activities that can be attributed to the inhibition of synthesis of prostaglandins and other mediators responsible for pain, inflammation and pyrexia.

Amygdalin, from Apricot Kernels, Induces Apoptosis and Causes Cell Cycle Arrest in Cancer Cells: An Updated Review

BACKGROUND Amygdalin is a cyanogenic glycoside which is described as a naturally occurring anticancer agent. Current review highlights apoptosis-inducing attributes of amygdalin towards different cancers and its potential application as an anti-cancer agent in cancer therapy. METHOD Data about amygdalin was retrieved from all major scientific databases i.e., PubMed, ScienceDirect, Google Scholar, Scopus and Medline by using combination of keywords like amygdalin, apoptosis, laetrile, vitamin B- 17, pro-apoptotic proteins, anti-apoptotic proteins, hydrogen cyanide, mechanism of action of amygdalin and amygdalin therapy on humans. However, no specific time frame was followed for collection of data. RESULTS Data collected from already published articles revealed that apoptosis is a central process activated by amygdalin in cancer cells. It is suggested to stimulate apoptotic process by upregulating expression of Bax (proapoptotic protein) and caspase-3 and downregulating expression of Bcl-2 (anti-apoptotic protein). It also promotes arrest of cell cycle in G0/G1 phase and decrease number of cells entering S and G2/M phases. Thus, it is proposed to enhance deceleration of cell cycle by blocking cell proliferation and growth. CONCLUSION The current review epitomizes published information and provides complete interpretations about all known anti-cancer mechanisms of amygdalin, possible role of naturally occurring amygdalin in fight against cancer and mistaken belief about cyanide toxicity causing potential of amygdalin. However, well-planned clinical trials are still needed to be conducted to prove effectiveness of this substance in vivo and to get approval for human use.

Pharmacological screening of Trachyspermum ammi for antihyperlipidemic activity in Triton X-100 induced hyperlipidemia rat model

Background: Mortality rate is increasing due to cardiovascular problems throughout the world. These cardiac problems are directly associated with dyslipidemia. Aim: The aim of this study was to evaluate the antihyperlipidemic effect of aqueous extract and methanol extract of Trachyspermum ammi at 1 g/kg, 3 g/kg, and 5 g/kg dose levels in rats. Materials and Methods: For this purpose, 45 male albino rats were used and randomly divided into nine equal groups (n = 5). The lipid levels were increased after 24 h of single intraperitoneal injection of Triton X-100 (100 mg/kg) in rats. Aqueous and methanol extracts equivalent to 1 g/kg, 3 g/kg, and 5 g/kg were administered orally to the rats for 21 days. Atorvastatin (10 mg/kg) was used as standard drug. Blood samples were collected at 0, 2nd, 9th, 16th, and 23rd day by a direct cardiac puncture in Vacuette® heparin tubes. Serum was separated and then analyzed for lipid profile, liver function test (LFT), and renal function test (RFT) using standard diagnostic kits. Results: Results showed that extracts at 3 g/kg and 5 g/kg decreased the levels of total cholesterol, triglyceride, and low-density lipoprotein and increased high-density lipoprotein concentration in serum. T. ammi also decreased LFT and RFT parameters at the end of the study. Conclusion: T. ammi possessed antioxidant and antihyperlipidemic activities along with hepato- and nephro-protective effects. Aqueous and methanol extracts of T. ammi were administered orally at 1-, 3-, and 5 g/kg doses to hyperlipidemic rats (Triton X-100 induced hyperlipidemia) and atorvastatin (10 mg/kg, orally) was used as standard drug. Methanol extract at 5 g/kg showed antihyperlipidemic effect that is identical to that of standard drug.

Chemical characterisation and hepatoprotective potential of Cosmos sulphureus Cav. and Cosmos bipinnatus Cav.

Abstract This study was conducted to validate the hepatoprotective activity of Cosmos sulphureus and Cosmos bipinnatus. Aqua-methanolic extracts of both plants were evaluated for the presence of various phyto-constituents through HPLC. Different doses of both plant extracts were administered to rats for nine days. Standard control was silymarin 100 mg/kg. Paracetamol 1 gm/kg was administered 3 h post treatment on 9th day for induction of hepatotoxicity. Blood was collected for the evaluation of liver biochemical markers and livers were removed for histopathological evaluation 24 h post-paracetamol treatment. HPLC analysis revealed the presence of quercetin, gallic acid, caffeic acid and chlorogenic acid in both plant extracts. The extracts of both plants decreased the level of alanine aminotransaminase and total bilirubin significantly (p < 0.05), dose dependently and protected hepatocytes from paracetamol-induced hepatotoxicity. It can be concluded that both plants may possess hepatoprotective activity possibly due to the presence of quercetin and phenolic compounds.

In Vivo Antioxidant Activity of Phyllanthus Emblicus against Cisplatin Induced Oxidative Stress in Mice

Method: oxidative stress was induced in micewith acute toxic dose (10 mg/kg) of cisplatin given i.p. Animals were divided into five groups (n = 5). Group I: negative control, group II: positive control group III and IV were given methanol extract ofPhyllanthus emblicus (250& 500 mg/kg; orally respectively) and group V was standard group receiving orally vitamin C & E (200 mg/kg each) for 20 days. On 21st day, animals were sacrificed and oxidative stress biomarkers were quantified.

Anti-angiogenic Potential of Mentha longifolia (Horse Mint): Chlorioallantoic Membrane Assay

Inhibition of angiogenesis is one of the mechanisms of action of anticancer drugs. The current study was designed to probe into anti-angiogenic effect of Mentha longifolia by employing Chorioallantoic membrane assay. White leghorn fertilized eggs were used in the study (n=10). On 6 day of incubation, aqueous solution of methanol extract (300-1000 μg/mL) of Mentha longifolia was applied to chicken embryos via CAM route. After 24 hours incubation, all eggs were opened carefully and CAM images were taken with camera. These images were loaded to SPIP software for quantification and assessment of structural changes in CAM. Blood vessels (primary, secondary and tertiary) diameters and CAM areas decreased in concentration dependent fashion in all treated groups as compared to values of control group. All embryos died at highest used concentration. It is concluded that methanol extract of Mentha longifolia possessed concentration dependent anti-angiogenic effect but toxic at 1000 μg/mL.