Current Pharmaceutical Biotechnology - Volume 19, Issue 14, 2018

Phenolic acids are secondary plant metabolites belonging to polyphenol classes, widely spread throughout the plant kingdom. The name “phenolic acids”, in general, describes phenols that possess one carboxylic acid functionality and they could be divided into three major subclasses: hydroxybenzoic, hydroxycinnamic and hydroxyphenylacetic acids. The great interest in phenolic acids is associated with their high potential for food preservation (antioxidant and antimicrobial activity) and, last but not least, high therapeutic potential. The aim of this review is to summarise the current knowledge concerning phenolic acids and the topics discussed include natural sources of phenolic acids, biosynthesis and metabolism, health benefits of phenolic acids (first of all the antioxidant activity of dietary phenolics and also anticarcinogenic and anti-inflammatory effect), their antimicrobial activity for selected groups of bacteria and fungi (yeasts) and structural modifications of the molecule especially those increasing lipophilicity and improving solubility in lipids. Recent advances in the methods of enzymatic synthesis of phenolic acid derivatives are described and some conclusions referring to Structure-Property-Activity Relationships of phenolic acids, particularly important from the point of view of their pharmaceutical and nutritional applications, are discussed.

Background: Epithelial ovarian cancer (EOC) is one of the most common cancers in the female reproductive system and deadliest gynecological cancer in the United States. Standard treatments by surgery and platinum-based chemotherapy are not satisfied for the patients with high risk of relapse. Advances in molecular biology for EOC development have brought several targeted therapies to benefit recurrent patients. Poly-ADP-ribose polymerase inhibitors (PARPi) may be one of the most successful classes of targeted therapies with three approved medicines. For better clinical outcomes and more comprehensive disease management of EOC, more novel classes of targeted therapies are needed. Method: We focus on non-PARPi novel targeted therapies that are completed or on-going in phase III clinical trials by searching databases of Pubmed and Clinicaltrials.gov. Keywords of “ovarian cancer, targeted therapy and phase III trial” were used for publications and information from May 2012 to May 2018. Results: There are total 150 viable EOC phase III studies listed in Clinicaltrials.gov., including 20 completed studies with results and 73 on-going studies. Bevacizumab plus chemotherapy is the only medication with government approval for recurrent EOC. Targeted therapies against other growthrelated factors, cytokines and folate receptor are failed in phase III trials or still on-going. Conclusion: Implications of on-going phase III trials are: 1) combination therapy of bevacizumab with atezolizumab may be the most anticipated studies for approvals; 2) mirvetuximab soravtansine plus chemotherapy may generate positive results to justify an approval; and 3) Immune therapy for EOC may bring new treatments for the patients.

There is a growing trend of herbal medicines in India as well as other parts of the world. The use of herbal medicines alone or alongside prescription drugs for disease management is quite common now. We hereby carry out a review of dominant species of Selinum mainly S. vaginatum C.B. Clarke and S. wallichianum (DC.) Raizada & H.O. Saxena which are potent source of herbal medicine and whose potential is still not exploited. They are found in Northern Himalayas in the states of Kashmir, Himachal Pradesh and Uttarakhand in India, and also distributed in adjoining countries like China, Nepal, and West Pakistan. It is a perennial, primitive, high altitude, therapeutic herbal plant belonging to family Apiaceae (Umbelliferae) traditionally used for various diseases like epilepsy, seizures, and hysteria, etc. The aim of this review was to provide a summary on botanical characterization, traditional uses, phytochemistry and pharmacological activity of Selinum spp. The available information will be further tapped for commercial use of this plant without endangering its status. Based on the available evidence on the species pharmacology and chemistry, we highlight in which their therapeutic potential can be properly harnessed for possible integration into the country's healthcare system and be further passed on globally.

Background: Colorectal cancer (CRC) is the second and third most frequent cancer in women and men, respectively; indeed, CRC is placed as the fourth world's most deadly cancer (after lung, liver, and stomach cancer). The incidence of CRC is strongly influenced by nutrition and the high fat/high carbohydrate Western-style diet. CRC is one of the most intensively studied cancer types, partly because of its high prevalence, but also because of the existence of its precursor lesions, tubular or villous adenomas, and more recently serrated adenomas. The morphological steps in the adenomacarcinoma sequence have been elucidated at a molecular level, which allow the identification of the genes responsible for CRC. Review and Conclusions: The main aim of this review is to provide data regarding the pathophysiological characteristics, molecular mechanisms as well as carcinogenic and chemopreventive agents for CRC, with emphasis on evidence supporting their efficacy. These compounds may modulate multiple signaling pathways involved in cell proliferation and apoptosis in transformed cells, they also enhance the host immune system and favor an effective treatment. Despite promising results from experimental studies, only a limited number of these compounds have been tested in clinical trials. The mechanistic spectrum and specificity of the action of phytochemicals represent a complex and evolving field of research.

Background: Standardized extract of Phyllanthus amarus has been shown to possess inhibitory effects on cellular and humoral immune responses in Wistar-Kyoto rats and Balb/c mice. Objective: In the present study, the standardized extract of P. amarus was investigated for its suppressive effects on type II collagen-induced rheumatoid arthritis (TCIA) in Sprague Dawley rats. Method: The major components of the extracts, lignans and phenolic compounds were analysed by using a validated reversed phase HPLC and LC-MS/MS. A rheumatoid arthritis rat model was induced by administering a bovine type II collagen emulsion subcutaneously at the base of tail, on day 0 and 7 of the experiment. Effects of the extract on severity assessment, changes in the hind paw volume, bone mineral density, body weight and body temperature were measured. Concentrations of cytokines (TNF-α, IL-1β, IL-1α, IL-6) released, matrix metalloproteinases (MMP-1, MMP-3 MMP-9) and their inhibitor (TIMP-1), haematological and biochemical changes were also measured. ELISA was used to measure the cytokines and proteinases in the rat serum and synovial fluid according to manufacturer's instructions. Results: The extract dose-dependently modulated the progression in physical parameters (i.e. decrease in body weight, increase in body temperature, reduced hind paw volume, reduced the severity of arthritis), bone mineral density, haematological and biochemical perturbations, serum cytokines production and levels of matrix metalloproteinases and their inhibitor in the synovial fluid. Histopathological examination of the knee joint also revealed that the extract effectively reduced synovitis, pannus formation, bone resorption and cartilage destruction. Conclusion: The results suggest that the oral administration of a standardized extract of P. amarus was able to suppress the humoral and cellular immune responses to type II collagen, resulting in the reduction of the development of TCIA in the rats.

Background: Pueraria candollei var. mirifica (P. candollei), known as White Kwao Krua in Thai, has long been used in traditional Thai medicine for the symptoms of menopause due to the potent estrogenic activity exhibited by the isoflavonoids and chromenes it contains. Recently, health hazards caused by P. candollei-derived products have arisen in Japan, and demands for analytical methods to standardize the P. candollei have been increasing. Previously, we have focused on quantifying the unique P. candollei-derived isoflavonoid kwakhurin (Kwa) and developed an indirect competitive enzyme- linked immunosorbent assay (icELISA) using a monoclonal antibody (MAb) against Kwa. However, MAb preparation requires the use of costly culture medium and sophisticated techniques. Objective and Method: In this study, we produced a recombinant antigen-binding fragment (Fab) against Kwa, as an alternative to MAb, for use in icELISA for quantitative analysis of Kwa. The VHCH1 and VL-CL proteins were individually expressed in Escherichia coli BL21 (DE3) strain and were then refolded to form active anti-Kwa Fab. Results and Conclusion: Characterization of anti-Kwa Fab revealed that it possessed high specificity (cross-reactivities with other Kwa-related compounds, <0.03%) and high sensitivity (limit of detection, 8.16 ng/mL). Additionally, validation analyses indicated that icELISA using anti-Kwa Fab is highly precise, accurate, and sufficiently reliable for use in quantitative analysis of Kwa. Consequently, an icELISA incorporating anti-Kwa Fab was developed for the analysis of P. candollei-derived products, to assure consumer safety.

CORRIGENDUM Corrigendum to Manuscript entitled Cytotoxic Effects and Production of Cytokines Induced by the Endophytic Paenibacillus polymyxa RNC-D In Vitro by Débora M. Neris1,3,*, Genoveva L.F. Luna2,3, Joice M. de Almeida Rodolpho1,3, Ana C. Urbaczek4, Ricardo de Oliveira Correia3, Karina A. Feitosa1,3, Nadja F.G. Serrano2,3, Cristina P. de Sousa2,3 and Fernanda de Freitas Anibal1,2,3. Curr. Pharm. Biotechnol., 2017; 18(9), 758-768. I hereby informed that all the authors agree with the inclusion of the name of the funding agency (FAPESP - Fundação de Amparo à Pesquisa do Estado de São Paulo) and the process number (2018/12846-5) to the acknowledgements section of the manuscript.