Tahir Mehmood

Anti-Helicobacter pylori and Urease Inhibition Activities of Some Traditional Medicinal Plants

Different parts of Acacia nilotica (L.) Delile, Calotropis procera (Aiton) W.T. Aiton, Adhatoda vasica Nees, Fagoniaar abica L. and Casuarina equisetifolia L. are traditionally used in folk medicine for the treatment of a variety of common ailments like nausea, cold, cough, asthma, fevers, diarrhea, sore throat, swelling, etc. The present study was aimed to evaluate the anti-Helicobacter pylori and urease inhibition activities of extracts produced from the above selected medicinal plants native to Soon Valley (home to an old civilization) in the Punjab province of Pakistan. Methanol, acetone and water extracts of the plants were evaluated for anti-bacterial activity against thirty four clinical isolates and two reference strains of H. pylori. Minimum inhibitory concentrations (MICs) of the extracts were determined using the agar dilution method and compared with some standard antibiotics like amoxicillin (AMX), clarithromycin (CLA), tetracycline (TET) and metronidazole (MNZ), used in the triple therapy for H. pylori eradication. H. pylori urease inhibition activity of the extracts was assessed by the phenol red method, wherein, Lineweaver-Burk plots were used to determine Michaelis-Menten constants for elucidating the mechanism of inhibition. Methanol and acetone extracts from Acacia nilotica and Calotropis procera exhibited stronger anti-H. pylori activity than MNZ, almost comparable activity with TET, but were found to be less potent than AMX and CLT. The rest of the extracts exhibited lower activity than the standard antibiotics used in this study. In the H. pylori urease inhibitory assay, methanol and acetone extracts of Acacia nilotica and Calotropis procera showed significant inhibition. Lineweaver-Burk plots indicated a competitive mechanism for extract of Acacia nilotica, whereas extract of Calotropis procera exhibited a mixed type of inhibition.

Deoxyelephantopin induces apoptosis in HepG2 cells via oxidative stress, NF‐κB inhibition and mitochondrial dysfunction

Deoxyelephantopin (DET), a naturally occurring sesquiterpene lactone present in Chinese medicinal herb, Elephantopus scaber has been shown to exert anti-inflammatory as well as anticancer effects in various cancer cells of human origin in vitro. However, the exact molecular mechanism underlying DET-induced apoptosis remains largely unexplored, particularly in human hepatocellular carcinoma G2 (HepG2) cells. In the present study, we found that DET inhibits proliferation and induces apoptosis in HepG2 cells in a dose-dependent manner. This DET-mediated apoptosis was found to be associated with reactive oxygen species generation, glutathione depletion and decreased activity of thioredoxin reductase, mitochondrial membrane potential disruption, Bcl-2 family proteins modulation, cytochrome c release, caspases-3 activation, PARP cleavage and inhibition of NF-κB activation. DET inhibited the constitutive as well as induced-translocation of NF-κB into nucleus and augmented the apoptotic effect of Gemcitabine. IKK-16 (NF-κB inhibitor) further enhanced the cytotoxicity of DET and gemcitabine indicating that DET induces apoptosis in HepG2 cells at least partially through inhibition of NF-κB activation. Further mechanistic study demonstrated that DET inhibits the translocation of constitutive as well as induced-NF-κB into nucleus by decreasing phosphorylation of IкBα. Moreover, pretreatment of cells with 3 mM NAC reversed DET-mediated cell death and NF-κB inhibition, indicating that DET exerts its anticancer effects mainly through oxidative stress. Therefore, DET may be developed into a lead chemotherapeutic drug as a single agent or in combination with clinical drugs for the effective treatment of liver cancer.

Deoxyelephantopin and Isodeoxyelephantopin as Potential Anticancer Agents with Effects on Multiple Signaling Pathways

Cancer is the 2nd leading cause of death worldwide. The development of drugs to target only one specific signaling pathway has limited therapeutic success. Developing chemotherapeutics to target multiple signaling pathways has emerged as a new prototype for cancer treatment. Deoxyelephantopin (DET) and isodeoxyelephantopin (IDET) are sesquiterpene lactone components of “Elephantopus scaber and Elephantopus carolinianus”, traditional Chinese medicinal herbs that have long been used as folk medicines to treat liver diseases, diabetes, diuresis, bronchitis, fever, diarrhea, dysentery, cancer, and inflammation. Recently, the anticancer activity of DET and IDET has been widely investigated. Here, our aim is to review the current status of DET and IDET, and discuss their anticancer activity with specific emphasis on molecular targets and mechanisms used by these compounds to trigger apoptosis pathways which may help to further design and conduct research to develop them as lead therapeutic drugs for cancer treatments. The literature has shown that DET and IDET induce apoptosis through multiple signaling pathways which are deregulated in cancer cells and suggested that by targeting multiple pathways simultaneously, these compounds could selectively kill cancer cells. This review suggests that DET and IDET hold promising anticancer activity but additional studies and clinical trials are needed to validate and understand their therapeutic effect to develop them into potent therapeutics for the treatment of cancer.

Electrochemical DNA biosensors: a review

This review aims to focus on recent reported research work on the construction and function of different electrochemical DNA biosensors. It also describes different sensing materials, chemistries of immobilization probes, conditions of hybridization and principles of transducing and amplification strategies.,The human disease-related mutated genes or DNA sequence detection at low cost can be verified by the electrochemical-based biosensor. A range of different chemistries is used by the DNA-based electrochemical biosensors, out of which the interactions of nanoscale material with recognition layer and a solid electrode surface are most interesting. A diversity of advancements has been made in the field of electrochemical detection.,Some important aspects are also highlighted in this review, which can contribute in the creation of successful biosensing devices in the future.,This paper provides an updated review of construction and sensing technologies in the field of biosensing.

The dual specificity role of transcription factor FOXO in type 2-diabetes and cancer

The FOXO (Forkhead box O) transcription factors are implicated in several signaling pathways and play a vital role in various cellular and physiological processes include for instance, ROS (reactive oxygen species) response, cell proliferation, regulation of programmed cell death, longevity, metabolism and cancer and regulation of cell cycle. In humans, the four FOXO family members are responsible for resemblance in their structure, regulation and functions. FOXO1 gene is highly expressed in adipose tissues and it affects the regulation of glycogenolysis and gluconeogenesis through insulin signaling. The gene of FOXO3 is highly expressed in the kidney, heart, spleen and brain and is characterized as diverse forkhead DNA-binding domain of transcription factors. The FOXO3 is a tumor suppressor gene and found to interact with p53, the trigger for apoptosis through BCl2 family genes and a regulator of Notch signaling pathway for the self-renewal of stem cells. Therefore, FOXOs remains to be a fascinating and potential target to acquire novel therapeutic approaches to cure cancer. This review will provide a comprehensive overview about the biology of FOXO proteins, which can be utilized for developing current therapeutic approaches to treat cancer.

Santamarine Inhibits NF-кB and STAT3 Activation and Induces Apoptosis in HepG2 Liver Cancer Cells via Oxidative Stress.

Sesquiterpene lactones have long been used in traditional Chinese medicines to treat inflammatory diseases. Recently, sesquiterpene lactone family compounds have been recognized as potential anticancer agents. Thus, it is necessary to explore new sesquiterpene lactones and their antitumor mechanism for cancer treatments. In the present study, we have explored the potential anti-cancer activity of a novel sesquiterpene lactone compound “santamarine” (STM) in HepG2 cells. It inhibited proliferation and induced apoptosis dose-dependently with IC50 ~ 70 μM. Induction of apoptosis was found to be linked with increased reactive oxygen species (ROS) generation, decreased activity of thioredoxin reductase (TrxR), glutathione (GSH) depletion, mitochondrial membrane potential (ΔΨm) dissipation, Bcl-2 family proteins modulation, cytochrome c release, caspases-9, -8 and -3 activation and PARP cleavage. Further mechanistic study demonstrated that STM inhibited the constitutive and TNF-α-induced translocation of NF-кB into nucleus by decreasing phosphorylation of IkB-α. Moreover, STM inhibited STAT3 activation by decreasing phosphorylation at tyrosine705. NAC pretreatment reversed the effect of STM-mediated cell death, NF-кB inhibition and blockage of STAT3 activity, indicating the involvement of oxidative stress in STM-mediated anticancer activity. Further studies are needed to explore the exact molecular mechanism of STM-induced apoptosis to develop it into a lead for treatment of liver cancer in future.