Efficacy of Bee Products(Anzer Honey,Pollen and Propolis)in Detection and Healing of Damage Induced by Antidiabetic Drug Vildagliptin/Metformin Hydrochloride in Healthy Human Pancreatic Cells:Cytotoxic,Genotoxic and Biochemical Studies

Background and Objective Although drugs are powerful therapeutic agents,they have a range of side effects.These side effects are sometimes cellular and not clinically noticeable.Vildagliptin/metformin hydrochloride is one of the most widely used oral antidiabetic drugs with two active ingredients.In this study,we investigated its harmful effects on the metabolic activation system in healthy human pancreatic cells“hTERT-HPNE”,and we aimed to improve these harmful effects by natural products.To benefit from the healing effect,we used the unique natural products produced by the bees of the Anzer Plateau in the Eastern Black Sea Region of Turkey.Methods Cytotoxic and genotoxic effects of the drug were investigated by different tests,such as MTT,flow cytometry-apoptosis and comet assays.Anzer honey,pollen and propolis were analyzed by gas chromatography/mass spectrometry(G/C-MS).A total of 19 compounds were detected,constituting 99.9%of the samples.Results The decrease in cell viability at all drug concentrations was statistically significant compared to the negative control(P<0.05).A statistically significant decrease was detected in the apoptosis caused by vildagliptin/metformin hydrochloride with the supplementation of Anzer honey,pollen and propolis in hTERT-HPNE cells(P<0.05).Conclusion This study can contribute to other studies testing the healing properties of natural products against the side effects of oral antidiabetics in human cells.In particular,Anzer honey,pollen and propolis can be used as additional foods to maintain cell viability and improve heal damage and can be evaluated against side effects in other drug studies.

Antimicrobial drug resistance of Staphylococcus aureus in dairy products

Objective:To evaluate the prevalence of multidrug resistant Staphylococcus aureus(S.aureus) in dairy products.Methods:Isolation and identification of S.aureus were performed in 3 dairybased food products.The isolates were tested for their susceptibility to 5 different common antimicrobial drugs.Results:Of 50 samples examined,5(10%) were contaminated with 5. aureus.Subsequently,the 5 isolates were subjected to antimicrobial resistance pattern using five antibiotic discs(methicillin,vancomycin,kanamycin,chloramphenicol and tetracycline).Sample 29 showed resistance to methicillin and vancomycin.Sample 18 showed intermediate response to tetracycline.The other samples were susceptible to all the antibiotics tested.Conclusions:The results provide preliminary data on sources of food contamination which may act as vehicles for the transmission of antimicrobial-resistant Staphylococcus.Therefore,it enables us to develop preventive strategies to avoid the emergence of new strains of resistant S.aureus.

The Success of Natural Products in Drug Discovery

Drug discovery leading to robust and viable lead candidates’ remains a challenging scientific task, which is the transition from a screening hit to a drug candidate, requires expertise and experience. Natural products and their derivatives have been recognized for many years as a source of therapeutic agents and of structural diversity. However, in addition to their chemical structure diversity and their biodiversity, the development of new technologies has revolutionized the screening of natural products in discovering new drugs. Applying these technologies compensates for the inherent limitations of natural products and offers a unique opportunity to re-establish natural products as a major source for drug discovery. The present article attempts to describe the utilization of compounds derived from natural resources as drug candidates, with a focus on the success of these resources in the process of finding and discovering new and effective drug compounds, an approach commonly referred to as “natural product drug discovery”.

Natural products as a crucial source of anti-inflammatory drugs: recent trends and advancements

Natural active molecules are key sources of modern innovative drugs. Particularly, a great amount of natural active molecules have been reported to possess promising therapeutic effects on inflammatory diseases, including asthma, rheumatoid arthritis, hepatitis, enteritis, metabolic disorders and neurodegenerative diseases. However, these natural active molecules with various molecular structures usually exert anti-inflammatory effects through diversiform pharmacological mechanisms, which is necessary to be summarized systematically. In this review, we introduced the current major anti-inflammatory natural active molecules based on their chemical structures, and discussed their pharmacological mechanisms including anti-inflammatory molecular signaling pathways and potential target proteins, which providing a referential significance on the development of novel anti-inflammatory drugs, and also revealing new therapeutic strategies for inflammatory diseases.

Anticancer drug screening of natural products:In vitro cytotoxicity assays,techniques,and challenges

Natural products include several diverse compounds that have been found to be effective against cancer.Discovering anticancer compounds in nature is a multistep and complex process that requires pre-clinical and clinical studies.Only a few of the available natural products are used to treat cancer since most of them have very high complexity and low bioavailability.Therefore,the process of anticancer drug discovery requires a straightforward and effective method to assess anticancer activity using in vitro assays.This review summarizes various cell-based assays and techniques used to measure cell viability,migration,and apoptosis,focusing in particular on the principles,mechanisms,advantages,and disadvantages of each assay to provide a preliminary platform for cancer drug discovery.

Exploring of drug leads from diversity-oriented Michael-acceptor library derived from natural products

A potential strategy for drug lead identification and in-active natural products re-discovery is elaborated.Starting from fifteen structurally diverse natural products,a focused library featured by Michael acceptors is constructed with IBX mediated oxidation.Biological assay on five tumor cell lines indicates that four Michael acceptors,8a,11a,12a,14a,are with improved cytotoxicity(3-10 folds more potent than the parent compounds),which merit further investigations.Further thiol-sensitive assay of the active hit 8a revealed that it was an irreversible Michael acceptor.The results suggest that the strategy is not only effective and relatively high discovery rate(28%),but also resource saving.

Effects of Maillard reaction and its product AGEs on aging and age-related diseases

Maillard reaction(MR)is a non-enzymatic browning reaction commonly seen in food processing,which occurs between reducing sugars and compounds with amino groups.Despite certain advantages based on Maillard reaction products(MRPs)found in some food for health and storage application have appeared,however,the MR occurring in human physiological environment can produce advanced glycation end products(AGEs)by non-enzymatic modification of macromolecules such as proteins,lipids and nucleic acid,which could change the structure and functional activity of the molecules themselves.In this review,we take AGEs as our main object,on the one hand,discuss physiologic aging,that is,age-dependent covalent cross-linking and modification of proteins such as collagen that occur in eyes and skin containing connective tissue.On the other hand,pathological aging associated with autoimmune and inflammatory diseases,neurodegenerative diseases,diabetes and diabetic nephropathy,cardiovascular diseases and bone degenerative diseases have been mainly proposed.Based on the series of adverse effects of accelerated aging and disease pathologies caused by MRPs,the possible harm caused by some MR can be slowed down or inhibited by artificial drug intervention,dietary pattern and lifestyle control.It also stimulates people's curiosity to continue to explore the potential link between the MR and human aging and health,which should be paid more attention to for the development of life sciences.

The 4th Euro-Mediterranean Conference of Natural Products and Drug Discovery: Back to Mother Nature (BioNat-IV), Cairo/Sharm El-Sheikh, Egypt, March 3–7, 2015

The 4 th Euro-Mediterranean Conference of Natural Products and Drug Discovery: Back to Mother Nature (Bio Nat-IV) was recently (from March 3 rd through 7 th, 2015) convened in Cairo and Sharm El-Sheikh along the Red Sea coast of Egypt. Overall, the meeting provided a platform for scientists from different nations to discuss emerging ideas that focused on cell signaling in cancer;the pathogenesis of autoimmune diseases;the identification and use of natural products as well as novel drug delivery approaches for the treatment of cancer,arthritis, diabetes, tuberculosis, fungal infection, etc.;and untapped or unconventional sources for natural products. This fourth in a row conference tried to bridge the gap not only between basic research and clinical applications, but also between developed nations and developing countries. With the continuing success of these past meetings, the fifth EuroMediterranean Conference of Natural Products and Drug Discovery(BioNat-V) is slated to be in February 2017.

Natural Products as Potential Lead Compounds for Drug Discovery Against SARS-CoV-2

For the past 2 years,the coronavirus responsible for the COVID-19 infection has become a world pandemic,ruining the lives and economies of several nations in the world.This has scaled up research on the virus and the resulting infection with the goal of developing new vaccines and therapies.Natural products are known to be a rich source of lead compounds for drug discovery,including against infectious diseases caused by microbes(viruses,bacteria and fungi).In this review article,we conducted a literature survey aimed at identifying natural products with inhibitory concentrations against the coronaviruses or their target proteins,which lie below 10μM.This led to the identification of 42 compounds belonging to the alkaloid,flavonoid,terpenoid,phenolic,xanthone and saponin classes.The cut off concentration of 10μM was to limit the study to the most potent chemical entities,which could be developed into therapies against the viral infection to make a contribution towards limiting the spread of the disease.

Development of Generic Drug Products by Pharmaceutical Industries Considering Regulatory Aspects: A Review

Development of generic drug product by pharmaceutical industry is a scientific and technical approach which is totally different from developing a reference or innovator product. Most of the developing countries focus on developing the generic drug products because huge amount of investment is required for innovation and to develop reference product. The generic medicine has to be bioequivalent to the innovator drug and ensure the same biological effect with proper safety and efficacy. Nowadays, the pharmaceutical industries focus on the development of generic product as this does not require that much time and cost compared to the innovator company. But development of generic product is also difficult as it contains the same therapeutic efficacy as innovator. The development approach is based on the target market, i.e. US market, EU market. If a manufacturer targets the US market, then all excipients should be USP grade, analysis should be conducted by USP method or in-house method and stability studies as well. Prior and during the development of generic drug product API selection, dosage form selection, reference product selection and characterization, formulation development, analytical method development, tech transfer or submission batch are prime concern. Then again, bioequivalence study, drug registration procedure and commercialization of the generic product considering regulatory guidance of respective regulatory agencies and the approaches taken by the regulatory agencies for the development of registration of generic medicines are also crucial as well for the development of generic drug product. The aim of this study was to review the entire stage of a generic drug development by a generic pharmaceutical company.

Current Perspective in the Discovery of Anti-aging Agents from Natural Products

Aging is a process characterized by accumulating degenerative damages,resulting in the death of an organism ultimately.The main goal of aging research is to develop therapies that delay age-related diseases in human.Since signaling pathways in aging of Caenorhabditis elegans(C.elegans),fruit flies and mice are evolutionarily conserved,compounds extending lifespan of them by intervening pathways of aging may be useful in treating age-related diseases in human.Natural products have special resource advantage and with few side effect.Recently,many compounds or extracts from natural products slowing aging and extending lifespan have been reported.Here we summarized these compounds or extracts and their mechanisms in increasing longevity of C.elegans or other species,and the prospect in developing antiaging medicine from natural products.

Natural Products in Cancer Therapy: Past, Present and Future

Natural products,with remarkable chemical diversity,have been extensively investigated for their anticancer potential for more than a half-century.The collective efforts of the community have achieved the tremendous advancements,bringing natural products to clinical use and discovering new therapeutic opportunities,yet the challenges remain ahead.With remarkable changes in the landscape of cancer therapy and growing role of cutting-edge technologies,we may have come to a crossroads to revisit the strategies to understand nature products and to explore their therapeutic utility.This review summarizes the key advancements in nature product-centered cancer research and calls for the implementation of systematic approaches,new pharmacological models,and exploration of emerging directions to revitalize natural products search in cancer therapy.

A Systemic Review on Topical Marketed Formulations, Natural Products, and Oral Supplements to Prevent Androgenic Alopecia: A Review

Androgens have an intense consequence on the human scalp and body hair.Scalp hair sprouts fundamentally in awol of androgens whereas the body hair hike is vulnerable to the activity of androgens.Androgenetic alopecia(AGA)invoked as males emulate Alopecia due to the cause of the dynamic reduction of scalp hair.Androgens are medium of terminus growth of hair although the body.Local and system androgens convert the extensive terminal follicles into lesser vellus like structure.The out start of this type of alopecia is intensely irregular and the reason behind this existence of enough circulating steroidal hormones androgens and due to genetic predisposition.Effective treatments are available in the market as well as under clinical and preclinical testing.Many herbal formulations are also available but not FDA approved.Different conventional and NDDS formulations are already available in the market.To avoid various systemic side effects of both Finasteride and Minoxidil,topical formulations and natural products(nutrients,minerals,vitamins)now a days are being widely used to treat Androgenic alopecia.CAM(complementary and alternative medicine)provides the option to elect favorable,low-risk,adjuvant and alternative therapies.Herein,we offer a widespread review of topical marketed formulations,natural products,and CAM treatment options for AGA.

Successful generic drug product development:From research to marketing approval

Recently,generic drug products have played an increasingly important role in the health care system globally,especially in the developing world,as they provide for an effective and more affordable alternative for healthcare professionals.Generic drug products are proven therapeutically equivalent to the corresponding innovator’s product,and hence can be substituted in clinical practice.The objective of generic drug development is to develop a stable and bioequivalent generic drug product with desirable properties in a timely manner.This presentation is intended to summarize three important sequential stages essential for successful generic drug development based on a regulatory experience in reviewing and evaluating the Pharmaceutical Development Section(P2)of the ASEAN Common Technical Dossier(ACTD)of generic drug product applications submitted to the Food and Drug Administration,Thailand[1,2].

Occurrence of <i>Escherichia coli</i>O157 in Retailed-Beef and Related Meat Products in Zaria, Nigeria

This study evaluated retailed-beef and related meat products for E. coli O157 in Zaria, Nigeria. Sample types included raw meat, “suya” (roasted meat), “balangu” (barbequed meat), “kilishi” (spiced sun dried meat) and “dambu” (shredded fried meat). A total of 182 samples were analyzed for E. coli O157. Isolates were characterized using conventional biochemical methods and Microbact 12E test kit. Susceptibilities of the isolates to 18 commonly used antimicrobial agents were determined by the disk diffusion method. The carriage of stx1 and stx2 genes was determined by PCR. Microbact confirmed 4 E. coli isolates. All isolates exhibited multiple drug resistance to the antimicrobial agents tested. An overall prevalence of 2.2% was obtained for E. coli O157. All 4 isolates of E. coli O157 were isolated from raw meat;two of which harboured the stx1 gene.

Effect of Homoeopathic Drugs to Control Growth and Production of <i>A. flavus</i>

Five common homoeopathic drugs viz., Belladonna, Bryonia, Colchicum, Colocynth and Lathyrus sat were selected and tested against growth and aflatoxin production of Aspergillus flavus. The result indicates that all five drugs suppressed the growth of A. flavus. The lower concentration of all the tested drugs induced maximum growth of fungi and maximum production of aflatoxin. However, the growth as well as aflatoxin production potentiality was considerably decreased when the concentration of the drug was increased. Out of all the five drugs, Bryonia was comparatively less effective with respect to inhibition in aflatoxin production. But Belladonna was found to be most effective drug on growth and aflatoxin production.

Marine natural products with anti-inflammation effects

The ocean possesses a complex setting with high pressure,high salinity,oligotrophy,low temperature and weak illumination conditions.To survive and evolve in such harsh surroundings,marine organisms metabolize a series of chemicals known as secondary metabolites which indicate structural and functional diversity to adapt interspecific survival competition.During recent decades,the anti-inflammatory property of marine natural products has come under scrutiny as inflammation involves in the vast majority of diseases.Correspondingly,a myriad of marine bioactive molecules including terpenes,polypeptides,polysaccharides,sterols and many others may bring a new insight into inflammation therapies with multifarious sources and minimal side effects.And a better understanding of their mechanisms of anti-inflammation may lead to better treatments for numerous diseases.Herein,the research progress of marine-derived anti-inflammation compounds and the relevant mechanisms were reviewed,to provide a basis for the research and development of anti-inflammatory marine drugs.

The Role of Medical Literature, Clinical Trials and Experimental Research in Drug Product-Injury Litigation: A Primer with Two Examples

When any type of product has been ordered to be removed from the marketplace by a governmental regulatory body, that action is a powerful indicator that the product has been determined to be unsafe for further use, thereby branding the product as defective and opening up the possibility of product liability litigation. When the product is a drug or medical device, it is especially serious since the possibility of personal injury (acute and/or chronic) or death may occur. Needless to say, in these situations, product injury litigation will almost surely follow. We review the definition and requisite claims needed to establish drug product liability, and the role that the medical literature, clinical trial data, and even experimental research data can play in product (drug)-injury litigation. We show how each of these resources played a significant role in two well-known cases: Fen-Phen and thimerosal. The ultimate goal of such knowledge is to make better informed decisions about drug safety.

Application of Liquid Chromatography-High Resolution Time-of-flight Mass Spectrometry in the Detection of Raw Milk and Dairy Products

Milk and dairy products are more and more popular with consumers due to their various nutrients, and their quality and safety issues have always been concerned. Therefore, the development of rapid, accurate and simple screening techniques is of great significance. Liquid chromatography-high resolution time-of-flight mass spectrometry has high-resolution and high-throughput detection functions, and has gradually begun to be applied in the detection of milk and dairy products. This paper summarized the application of milk and dairy products in liquid chromatography-high resolution time-of-flight mass spectrometry, laying a foundation for the development of new methods.

Antibiotic residues in milk and milk products:A momentous challenge for the pharmaceutical industry and medicine

Dairy products are nutritious food items that contain various essential nutrients,however,it has been proven that residual antibiotics have contaminated such products.These residues can cause several side effects on human health.They increase antimicrobial resistance against several threatening microorganisms,as well as significant growth in allergenic reactions.Various methods,including heat treatments,have been applied to alleviate and reduce the effect of antibiotic residue level in milk and milk products.Changes in drug levels were not sig-nificantly remarkable,obliging researchers to find new approaches to prevent or reduce their risk and limit their complications on human health.