Current Pharmaceutical Biotechnology - Volume 21, Issue 5, 2020

Background: Natural products are the rootstock for identifying new drugs since ancient times. In comparison with synthetic drugs, they have abounding beneficial effects in bestowing protection against many diseases, including cancer. Cancer has been observed as a major threat in recent decades, and its prevalence is expected to increase over the next decades. Also, current treatment methods in cancer therapy such as radiation therapy and chemotherapy cause severe adverse side effects among the cancer population. Therefore, it is exigent to find a remedy without any side effects. Methods: In recent years, research has focused on obtaining naturally derived products to encounter this complication. The current pace of investigations, such as gene identification and advancement in combinatorial chemistry, leads to the aberrant access to a wide range of new synthetic drugs. In fact, natural products act as templates in structure predictions and synthesis of new compounds with enhanced biological activities. Results: Recent developments in genomics have established the importance of polymorphism, which implies that patients require different drugs for their treatment. This demands the discovery of a large number of drugs, but limited sources restrict the pharmaceutical industry to overcome these major obstacles. The use of natural products and their semisynthetic and synthetic analogues could alleviate these problems. However, the lack of standardization in terms of developing methods for evaluating the chemical composition, efficacy, isolation and international approval is still a major limitation in this field. In the past few years, several drug-approval authorities, including the FDA and WHO have allowed using these naturally derived compounds in humans. Conclusion: In this review, we described the use of some natural products from plant and marine sources in cancer treatment and shed some light on semi-synthetic and synthetic compounds derived from natural sources used in cancer therapy.

Background: Bacteriophages are viruses, which are obligate parasites of specific bacteria for the completion of their lifecycle. Bacteriophages could be the possible alternative to antibioticresistant bacterial diseases. With this objective, extensive research in different fields is published which are discussed in this article. Methods: After a review of bacteriophage therapy, bacteriophages were found to be effective against the multidrug-resistant bacteria individually or synergistically with antibiotics. They were found to be more effective, even better than the bacteria in the development of a vaccine. Results: Apart from the bacteriophages, their cell contents like Lysin enzymes were found equally very much effective. Only the major challenge faced in phage therapy was the identification and characterization of bacteria-specific phages due to the wide genetic diversity of bacterial populations. Similarly, the threshold level of bacteriophages to act effectively was altered by ultraviolet radiation and heat exposure. Conclusion: Thus, bacteriophage therapy offers promising alternatives in the treatment of antibioticresistant bacteria in different fields. However, their effectiveness is determined by a triad of bacteriophages (type & quantity), host (bacteria) and environmental factors.

Background: Treatment of neurological diseases using systemic and non-surgical techniques presents a significant challenge in medicine. This challenge is chiefly associated with the condensation and coherence of the brain tissue. Methods: The coherence structure of the brain is due to the presence of the blood-brain barrier (BBB), which consists of a continuous layer of capillary endothelial cells. The BBB prevents most drugs from entering the brain tissue and is highly selective, permitting only metabolic substances and nutrients to pass through. Results: Although this challenge has caused difficulties for the treatment of neurological diseases, it has opened up a broad research area in the field of drug delivery. Through the utilization of nanoparticles (NPs), nanotechnology can provide the ideal condition for passing through the BBB. Conclusion: NPs with suitable dimensions and optimum hydrophobicity and charge, as well as appropriate functionalization, can accumulate in the brain. Furthermore, NPs can facilitate the targeted delivery of therapeutics into the brain areas involved in Alzheimer’s disease, Parkinson’s disease, stroke, glioma, migraine, and other neurological disorders. This review describes these methods of actively targeting specific areas of the brain.

Background: Endophytic bacteria produce various bioactive secondary metabolites, which benefit human health. Tamarindus indica L. is well known for its medicinal value in human health care. Several studies have reported on its biological effects from various parts of T. indica, but only a few studies have been devoted to examining the biological activity of endophytes of T. indica. Objectives: In the present study, an endophyte was isolated from the leaves of T. indica and screened for its antimicrobial potential. Methods: The selected endophyte was identified by 16s rRNA partial genome sequencing and investigated for their antimicrobial potency. The preliminary phytochemical tests were conducted for the affirmation of phytoconstituents in the endophytic crude ethyl acetate extract of T. indica (TIM) and total phenolic content was performed. The antimicrobial potential of TIM was evaluated against human pathogenic ATCC gram-positive and gram-negative bacterial strains. Results: TIM exhibited an appreciable amount of gallic acid equivalent phenolic content (21.6 ± 0.04 mg GAE/g of crude extract). TIM showed the Minimum Inhibitory Concentration (MIC) at 250 μg/mL and Minimum Bactericidal Concentration (MBC) at 500 μg/mL among the selected human pathogenic ATCC strains. At MIC of 500 μg/mL, TIM displayed a significant zone of inhibition against P. aeruginosa and N. gonorrhoeae. Conclusion: The results from our study highlighted for the first time the antimicrobial potential of endophytic bacterial strain Bacillus velezensis in T. indica leaves and it could be further explored as a source of natural antimicrobial agents.

Background: Peripheral neuropathy can significantly impact the quality of life for those who are affected, as therapies from the current treatment algorithm often fail to deliver adequate symptom relief. There has, however, been an increasing body of evidence for the use of cannabinoids in the treatment of chronic, noncancer pain. The efficacy of a topically delivered cannabidiol (CBD) oil in the management of neuropathic pain was examined in this four-week, randomized and placebocontrolled trial. Methods: In total, 29 patients with symptomatic peripheral neuropathy were recruited and enrolled. 15 patients were randomized to the CBD group with the treatment product containing 250 mg CBD/3 fl. oz, and 14 patients were randomized to the placebo group. After four weeks, the placebo group was allowed to crossover into the treatment group. The Neuropathic Pain Scale (NPS) was administered biweekly to assess the mean change from baseline to the end of the treatment period. Results: The study population included 62.1% males and 37.9% females with a mean age of 68 years. There was a statistically significant reduction in intense pain, sharp pain, cold and itchy sensations in the CBD group when compared to the placebo group. No adverse events were reported in this study. Conclusion: Our findings demonstrate that the transdermal application of CBD oil can achieve significant improvement in pain and other disturbing sensations in patients with peripheral neuropathy. The treatment product was well tolerated and may provide a more effective alternative compared to other current therapies in the treatment of peripheral neuropathy.

Background: This investigation was designed to evaluate the chemical composition, antioxidant, anti-inflammatory, genotoxicity, and antimicrobial activities of Curcuma caesia Roxb rhizome essential oil. Methods: Gas Chromatography/Mass Spectroscopy (GC/MS) analysis was performed to determine the chemical composition, standard antioxidative test DPPH assay, reducing power assay, in vitro antiinflammatory activity (egg albumin denaturation, protease inhibitory assay) by using standard methods. Similarly, antimicrobial activity was tested using the disc diffusion method, minimum inhibitory concentration ability (MIC); while to test genotoxicity, Allium cepa assay was used. Results: GC/MS analysis revealed eucalyptol (28.55%), epicurzerenone (19.62%), and camphor (21.73%) as the major components of C. caesia rhizome essential oil. Potent antioxidant (IC50= 48.08±0.003 μg/mL), anti-inflammatory (IC50= 121.7±0.0013 μg/mL), and antimicrobial activities of the essential oil were recorded better than the standard drugs Fluconazole for fungus and Ciprofloxacin for bacteria. The essential oil also possessed a strong antibacterial effect against two tested bacterial strains B. subtilis and B. cereus with 7.5 μg/mL MIC value, while for fungal strains the essential oil was most effective against S. cereviaceae with an MIC value of 2.5 μg/mL. All the data were recorded in triplicates. Allium cepa assay revealed minor genotoxicity with mitotic index, MI= 27.70%; chromosome aberration, A= 1.1% of C. caesia rhizome essential oil. Conclusion: C. caesia rhizome essential oil possesses potent antioxidant, anti-inflammatory, and antimicrobial properties with negligible genotoxicity. Hence, the present study is highly significant for the utilization of rhizome of C. caesia, a high-value ethnopharmacological plant for advanced R & D and commercial application.

Background: The plant species Thymus algeriensis (TA); Thymus capitatus (TC) and Rosmarinus officinalis (RO), are widely used in traditional medicine in Tunisia. The bioactivities of their essential oils have also been reported previously. The main objective of this work was to assess the phytochemical composition, the antioxidant activity, cytotoxic potential and the antibacterial, antifungal, of the essential oil (EO) of these plants. Methods: Gas Chromatography-Mass Spectrometry (GC-MS) was used to identify and quantify the constituents of the tested EO. Chemical tests, and spectrophotometric methods were used for antioxidant activities and for the screening and quantification of phytochemicals. The cytotoxic potential of the EO was checked using HCT 116 cultures. The extracts were evaluated for their antibacterial potential by the microdilution method. Antifungal activities were tested using the Poisoned food technique against Aspergillus niger and Aspergillus flavus. Results: The EO of tested plants presented several components, mainly monoterpenes and sesquiterpenes. The results revealed that T. capitatus EO is not toxic compared to the other tested samples. Phenolic compounds were detected and this EO showed excellent antioxidant activity presenting dosedependent relationship. Regarding antimicrobial activity, T. capitatus EO, also had the highest inhibition against all tested bacteria and fungi. Conclusion: This study showed the importance of the bioactivities (antioxidant, antimicrobial, and safety potential) of EOs of the plant species TC, RO, and TA used in traditional medicine.

Background: Snakes feed on germ-infested rodents, while water monitor lizards thrive on rotten matter in unhygienic conditions. We hypothesize that such creatures survive the assault of superbugs and are able to fend off disease by producing antimicrobial substances. In this study, we investigated the potential antibacterial activity of sera/lysates of animals living in polluted environments. Methods: Snake (Reticulatus malayanus), rats (Rattus rattus), water monitor lizard (Varanus salvator), frog (Lithobates catesbeianus), fish (Oreochromis mossambicus), chicken (Gallus gallus domesticus), and pigeon (Columba livia) were dissected and their organ lysates/sera were collected. Crude extracts were tested for bactericidal effects against neuropathogenic E. coli K1, methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pyogenes, Pseudomonas aeruginosa, Bacillus cereus and Klebsiella pneumoniae. To determine whether lysates/sera protect human cells against bacterialmediated damage, cytotoxicity assays were performed by measuring lactate dehydrogenase release as an indicator of cell death. Lysates/sera were partially characterized using heat-treatment and pronasetreatment and peptide sequences were determined using the Liquid Chromatography Mass Spectrometry (LC-MS). Results: Snake and water monitor lizard sera exhibited potent broad-spectrum bactericidal effects against all bacteria tested. Heat inactivation and pronase-treatment inhibited bactericidal effects indicating that activity is heat-labile and pronase-sensitive suggesting that active molecules are proteinaceous in nature. LCMS analyses revealed the molecular identities of peptides. Conclusion: The results revealed that python that feeds on germ-infested rodents and water monitor lizards that feed on rotten organic waste possess antibacterial activity in a heat-sensitive manner and several peptides were identified. We hope that the discovery of antibacterial activity in the sera of animals living in polluted environments will stimulate research in finding antibacterial agents from unusual sources as this has the potential for the development of novel strategies in the control of infectious diseases.

Background: Antifungal cyclic lipopeptides, bioactive metabolites produced by many species of the genus Bacillus, are promising alternatives to synthetic fungicides and antibiotics for the biocontrol of human pathogenic fungi. In a previous study, the co- production of five antifungal lipopeptides homologues (designated as AF1, AF2, AF3, AF4 and AF5) by the producer strain Bacillus subtilis RLID 12.1 using unoptimized medium was reported; though the two homologues AF3 and AF5 differed by 14 Da and in fatty acid chain length were found effective in antifungal action, the production/ yield rate of these two lipopeptides determined by High-Performance Liquid Chromatography was less in the unoptimized media. Methods: In this study, the production/yield enhancement of the two compounds AF3 and AF5 was specifically targeted. Following the statistical optimization (Plackett-Burman and Box-Behnken designs) of media formulation, temperature and growth conditions, the production of AF3 and AF5 was improved by about 25.8- and 7.4-folds, respectively under static conditions. Results: To boost the production of these two homologous lipopeptides in the optimized media, heat-inactivated Candida albicans cells were used as a supplement resulting in 34- and 14-fold increase of AF3 and AF5, respectively. Four clinical Candida auris isolates had AF3 and AF5 MICs (100 % inhibition) ranging between 4 and 16 μg/ml indicating the lipopeptide’s clinical potential. To determine the in vitro pharmacodynamic potential of AF3 and AF5, time-kill assays were conducted which showed that AF3 (at 4X and 8X concentrations) at 48h exhibited mean log reductions of 2.31 and 3.14 CFU/ml of C. albicans SC 5314, respectively whereas AF5 at 8X concentration showed a mean log reduction of 2.14 CFU/ml. Conclusion: With the increasing threat of multidrug-resistant yeasts and fungi, these antifungal lipopeptides produced by optimized method promise to aid in the development of novel antifungal that targets disease-causing fungi with improved efficacy.