Adeeb Shehzad

Role of traditional Islamic and Arabic plants in cancer therapy

Ethno pharmacological relevance This review article underlines individual Traditional Islamic and Arabic plant (TAI) and their role in treating cancer. The aim of the study is to specifically evaluate the progress of herbs, Arabic and Islamic traditional herbs in particular, applied in cancer treatment, so far. Materials and methods Islamic and Arabic plants were selected and identified through different literature survey using “Google scholar”, “Web of science”, “Scopus” and “PubMed”. Each plant, from identified Arabic and Islamic plants list, was search individually for the most cited articles in the aforementioned databases using the keywords, “Anticancer”, “Uses in cancer treatment”, “Ethno pharmacological importance in cancer” etc. Results The current review about Islamic and Arabic plants illuminates the importance of Islamic and Arabic plants and their impact in treating cancer. There is a long list of Islamic and Arabic plants used in cancer as mentioned in review with enormous amount of literature. Each plant has been investigated for its anticancer potential. The literature survey as mentioned in table shows; these plants are widely utilized in cancer as a whole, a part thereof or in the form of isolated chemical constituent. Conclusions This review strongly supports the fact; Arabic and Islamic traditional plants have emerged as a good source of complementary and alternative medicine in treating cancer. Traditional Arab-Islamic herbal-based medicines might be promising for new cancer therapeutics with low toxicity and minimal side effects. The plants used are mostly in crude form and still needs advance research for the isolation of phytochemicals and establishing its cellular and molecular role in treating cancer.

Therapeutic potential of curcumin for multiple sclerosis

Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system (CNS), characterized by demyelination, neuronal injury, and breaching of the blood-brain barrier (BBB). Epidemiological studies have shown that immunological, genetic, and environmental factors contribute to the progression and development of MS. T helper 17 (Th17) cells are crucial immunological participant in the pathophysiology of MS. The aberrant production of IL-17 and IL-22 by Th17 cells crosses BBB promotes its disruption and interferes with transmission of nerve signals through activation of neuroinflammation in the CNS. These inflammatory responses promote demyelination through transcriptional activation of signal transducers and activators of transcription-1 (STAT-1), nuclear factor kappa-B (NF-κB), matrix metalloproteinases (MMPs), interferon ϒ (IFNϒ), and Src homology region 2 domain-containing phosphatase-1 (SHP-1). B cells also contribute to disease progression through abnormal regulation of antibodies, cytokines, and antigen presentation. Additionally, oxidative stress has been known as a causative agent for the MS. Curcumin is a hydrophobic yellowish diphenolic component of turmeric, which can interact and modulate multiple cell signaling pathways and prevent the development of various autoimmune neurological diseases including MS. Studies have reported curcumin as a potent anti-inflammatory, antioxidant agent that could modulate cell cycle regulatory proteins, enzymes, cytokines, and transcription factors in CNS-related disorders including MS. The current study summarizes the reported knowledge on therapeutic potential of curcumin against MS, with future indication as neuroprotective and neuropharmacological drug.

Decursinol angelate inhibits PGE2-induced survival of the human leukemia HL-60 cell line via regulation of the EP2 receptor and NFκB pathway

ABSTRACT Decursinol angelate (DA), an active pyranocoumarin compound from the roots of Angelica gigas, has been reported to possess anti-inflammatory and anti-cancer activities. In a previous study, we demonstrated that prostaglandin E2 (PGE2) plays a survival role in HL-60 cells by protecting them from the induction of apoptosis via oxidative stress. Flow cytometry and Hoechst staining revealed that PGE2 suppresses menadione-induced apoptosis, cell shrinkage, and chromatin condensation, by blocking the generation of reactive oxygen species. Treatment of DA was found to reverse the survival effect of PGE2 as well as restoring the menadione-mediated cleavage of caspase-3, lamin B, and PARP. DA blocked PGE2-induced activation of the EP2 receptor signaling pathway, including the activation of PKA and the phosphorylation of CREB. DA also inhibited PGE2-induced expression of cyclooxygenase-2 and the activation of the Ras/Raf/ Erk pathway, which activates downstream targets for cell survival. Finally, DA greatly reduced the PGE2-induced activation of NF-κB p50 and p65 subunits. These results elucidate a novel mechanism for the regulation of cell survival and apoptosis, and open a gateway for further development and combinatory treatments that can inhibit PGE2 in cancer cells.

Phytochemical analysis and effects of Pteris vittata extract on visual processes

The present study was designed to explore the possible effects of Pteris vittata on visual sensitivity, ERG waves, and other components of the visual system. Electrophysiological techniques including electroretinography (ERG) were used in the present study. The phytochemical composition of the extract was investigated using liquid chromatography–mass spectrometry (LC–MS) techniques. The results indicated that the extract significantly augmented dark- and light-adapted ERG b-wave amplitude. Furthermore, these findings showed that P. vittata extract does not have Gamma-aminobutyric acid receptor antagonistic activity but may function as a retinal neural antagonist in bullfrog retina. P. vittata extract improved the visual sensitivity by 0.8 log unit of light intensity, and reduced the regeneration time for rhodopsin. The six main peaks obtained through LC–MS were identified as flavonoids. Based on these results, it was concluded that P. vittata extract or its constituents may be used to treat eye diseases.

Decursin and decursinol angelate: molecular mechanism and therapeutic potential in inflammatory diseases

Epidemiological studies have shown that inflammation plays a critical role in the development and progression of various chronic diseases, including cancers, neurological diseases, hepatic fibrosis, diabetic retinopathy, and vascular diseases. Decursin and decursinol angelate (DA) are pyranocoumarin compounds obtained from the roots of Angelica gigas. Several studies have described the anti-inflammatory effects of decursin and DA. Decursin and DA have shown potential anti-inflammatory activity by modulating growth factors such as vascular endothelial growth factor, transcription factors such as signal transducer and activator of transcription 3 and nuclear factor kappa-light-chain-enhancer of activated B cells, cellular enzymes including matrix metalloproteinases cyclooxygenase, and protein kinases such as extracellular receptor kinase, phosphatidylinositol-3-kinase, and protein kinase C. These compounds have the ability to induce apoptosis by activating pro-apoptotic proteins and the caspase cascade, and reduced the expression of anti-apoptotic proteins such as B-cell lymphoma 2 and B-cell lymphoma-extra-large. Interaction with multiple molecular targets and cytotoxic effects, these two compounds are favorable candidates for treating various chronic inflammatory diseases such as cancers (prostate, breast, leukemia, cervical, and myeloma), rheumatoid arthritis, diabetic retinopathy, hepatic fibrosis, osteoclastogenesis, allergy, and Alzheimer’s disease. We have summarized the preliminary studies regarding the biological effects of decursin and DA. In this review, we will also highlight the functions of coumarin compounds that can be translated to a clinical practice for the treatment and prevention of various inflammatory ailments.

PRP4 kinase induces actin rearrangement and epithelial-mesenchymal transition through modulation of the actin-binding protein cofilin

ABSTRACT Cell actin cytoskeleton is primarily modulated by Rho family proteins. RhoA regulates several downstream targets, including Rho‐associated protein kinase (ROCK), LIM‐Kinase (LIMK), and cofilin. Pre‐mRNA processing factor 4B (PRP4) modulates the actin cytoskeleton of cancer cells via RhoA activity inhibition. In this study, we discovered that PRP4 over‐expression in HCT116 colon cancer cells induces cofilin dephosphorylation by inhibiting the Rho‐ROCK‐LIMK‐cofilin pathway. Two‐dimensional gel electrophoresis, and matrix‐assisted laser desorption/ionization time‐of‐flight mass‐spectrometry (MALDI‐TOF MS) analysis indicated increased expression of protein phosphatase 1A (PP1A) in PRP4‐transfected HCT116 cells. The presence of PRP4 increased the expression of PP1A both at the mRNA and protein levels, which possibly activated cofilin through dephosphorylation and subsequently modulated the cell actin cytoskeleton. Furthermore, we found that PRP4 over‐expression did not induce cofilin dephosphorylation in the presence of okadaic acid, a potent phosphatase inhibitor. Moreover, we discovered that PRP4 over‐expression in HCT116 cells induced dephosphorylation of migration and invasion inhibitory protein (MIIP), and down‐regulation of E‐cadherin protein levels, which were further restored by the presence of okadaic acid. These findings indicate a possible molecular mechanism of PRP4‐induced actin cytoskeleton remodeling and epithelial‐mesenchymal transition, and make PRP4 an important target in colon cancer. HIGHLIGHTSPRP4 is involved in pre‐mRNA splicing and cell signalling.PRP4 modulates the actin cytoskeleton of cancer cells via RhoA activity inhibition.PRP4 induces cofilin dephosphorylation by inhibiting the Rho‐ROCK‐LIMK‐cofilin pathway in HCT116 cells.Dephosphorylation of cofilin results in F‐actin stabilization, re‐distribution of cytoplasmic actin, formation of actin stress fibers, and inhibition of cell motility.PRP4 over‐expression induces the expressions of PP1A, which directly or indirectly dephosphorylates cofilin, resulting in actin cytoskeleton rearrangement, downregulation of E‐cadherin, and EMT induction. Cofilin activation may be associated with EMT properties, and promotes the progression of human colon cancer.

Failure of Chemotherapy in Hepatocellular Carcinoma Due to Impaired and Dysregulated Primary Liver Drug Metabolizing Enzymes and Drug Transport Proteins: What to Do?

BACKGROUND Most of the drugs are metabolized in the liver by the action of drug metabolizing enzymes. In hepatocellular carcinoma (HCC), primary drug metabolizing enzymes are severely dysregulated, leading to failure of chemotherapy. Sorafenib is the only standard systemic drug available, but it still presents certain limitations, and much effort is required to understand who is responsive and who is refractory to the drug. Preventive and therapeutic approaches other than systemic chemotherapy include vaccination, chemoprevention, liver transplantation, surgical resection, and locoregional therapies. OBJECTIVES This review details the dysregulation of primary drug metabolizing enzymes and drug transport proteins of the liver in HCC and their influence on chemotherapeutic drugs. Furthermore, it emphasizes the adoption of safe alternative therapeutic strategies to chemotherapy. CONCLUSION The future of HCC treatment should emphasize on understanding of resistance mechanisms and the finding of novel, safe, and efficacious therapeutic strategies, which will surely benefit patients affected by advanced HCC.

Effect of Methanolic Extract of Dandelion Roots on Cancer Cell Lines and AMP-Activated Protein Kinase Pathway

Ethnomedicinal knowledge of plant-derived bioactives could help us in discovering new therapeutic compounds of great potential. Certainly, dandelion has been used in traditional ethno-medicinal systems (i.e., Chinese, Arabian, Indian, and Native American) to treat different types of cancer. Though, dandelion is highly vigorous, but the potential mode of action is still unclear. In the current study, the antiproliferative activity of methanolic extracts of dandelion root (MEDr) on cell viability of HepG2, MCF7, HCT116, and normal Hs27 was investigated. It was observed that MEDr (500 μg/mL) drastically decreased the growth of HepG2 cell line, while the effect on MCF7 and HCT116 cell lines was less pronounced and no effect has been observed in Hs27 cell lines. The MEDr also enhanced the phosphorylation level of AMPK of HepG2 cells, which considered crucial in cancer treatment and other metabolic diseases. The AMPK activation by MEDr noticed in the current study has never been reported previously. The results regarding the number of apoptotic cells (HepG2 cells) were in line with the cell viability test. The current observations clearly demonstrated the potency of MEDr against liver cancer with validation that dandelion could control AMPK and thus cancer in the treated cell lines.

Prostaglandin E2 inhibits resveratrol-induced apoptosis through activation of survival signaling pathways in HCT-15 cell lines

The COX-2 metabolite prostaglandin E2 (PGE2) promotes inflammation and progression of several cancers, including colon cancer. Resveratrol (3,5,4′-trihydroxy-trans-stilbene) induces apoptosis in cell lines and inhibits the invasion and metastasis of human colon cancer. PGE2 inhibits resveratrol-induced cell death; however, the underlying mechanisms are poorly understood. Therefore, the present study investigates the protection and survival effect of PGE2 against resveratrol-induced apoptosis in a human colorectal carcinoma (HCT-15) cell line. HCT-15 cells were treated with resveratrol and/or PGE2, and apoptotic cell death was assessed based on flow cytometry and the generation of reactive oxygen species (ROS). Resveratrol reduced HCT-15 cell viability and induced cell death through the production of ROS and the activation of caspase-3. Resveratrol treatment degraded poly (ADP-ribose) polymerase (PARP) in response to caspase-3 cleavage. Resveratrol treatment also decreased the activation of Ras-Raf-Erk and nuclear factor-κB (NF-κB) pathways and downregulated COX-2 expression, but did not regulate the secretion of extracellular PGE2. However, PGE2 exposure reversed resveratrol-induced oxidative stress and apoptosis, possibly through activation of the Ras-Raf-Erk pathway. PGE2 also positively regulated NF-κB activation and markedly increased the nuclear appearance of p50 and p65 subunits. Thus, this study provides insight into the mechanisms of resveratrol-induced apoptosis. Our results suggest that the inhibition of PGE2 and PGE2-induced activation of Ras-Raf-Erk and NF-κB signaling pathways may provide an alternative therapeutic strategy for the treatment and prevention of colon cancer.

Phytotherapy in the Management of Diabetes and Hypertension

Description: Phytotherapy in the Management of Diabetes and Hypertension is a good addition to existing volumes detailing knowledge of hyperglycemia therapy. This e-book emphasizes the basic biochemistry behind diabetes mellitus and hypertension, along with the control or remediation of these conditions through a cost effective, safe, easy-going, easy-adaptable method validated by scientific research. This e-book contains 7 chapters dealing with various aspects of these diseases and their Phytotherapy treatment and life style management. Phytotherapy can give patients long term benefits with less or no side effects. Hence, this e-book is an authentic alternative or complementary therapeutic compendium to physicians and patients. This book will also be useful to students, teachers, researchers, clinicians and general readers interested in learning about applied phytotherapy.