Advancements of gene therapy in cancer treatment: A comprehensive review.

Cancer is the main contributor for mortality in the world. Conventional therapy that available as the treatment options are chemotherapy, radiotherapy and surgery. However, these treatments are hardly cell-specific most of the time. Nowadays, extensive research and investigations are made to develop cell-specific approaches prior to cancer treatment. Some of them are photodynamic therapy, hyperthermia, immunotherapy, stem cell transplantation and targeted therapy. This review article will be focusing on the development of gene therapy in cancer. The objective of gene therapy is to correct specific mutant genes causing the excessive proliferation of the cell that leads to cancer. There are lots of explorations in the approach to modify the gene. The delivery of this therapy plays a big role in its success. If the inserted gene does not find its way to the target, the therapy is considered a failure. Hence, vectors are needed and the common vectors used are viral, non viral or synthetic, polymer based and lipid based vectors. The advancement of gene therapy in cancer treatment will be focussing on the top three cancer cases in the world which are breast, lung and colon cancer. In breast cancer, the discussed therapy are CRISPR/Cas9, siRNA and gene silencing whereas in colon cancer miRNA and suicide gene therapy and in lung cancer, replacement of tumor suppressor gene, CRISPR/Cas9 and miRNA.

Silver nanoparticles biogenically synthesised using Maclurodendron porteri extract and their bioactivities.

Silver nanoparticle is widely used in various field including medical, cosmetic, food and industrial purposes due to their unique properties in electrical conductivity, thermal, and biological activities. In the medical field, silver nanoparticles (AgNPs) have been reported to have strong antimicrobial and cytotoxic activities. This study aimed to synthesize and characterize silver nanoparticles (AgNPs) using Maclurodendron porteri (MP) extract and to evaluate the antimicrobial and cytotoxic activities of the synthesised MP-AgNPs. Green method of Ultrasound Assisted Extraction (UAE) was used to extract the leaves of M. porter. Liquid Chromatography -Mass Spectrometry/Quadrupole time-of-flight (LC-MS/QTOF) was used to identify the compounds in the leaf extract of M. porteri. Characterisation of the synthesised nanoparticles involved ultraviolet-visible (UV-Vis), Fourier Transform Infrared (FTIR), scanning electromagnetic microscopy (SEM), Zeta potential Analyzer and Particle Size Analyzer. The cytotoxic assay was conducted on MCF-7 and Caco-2 cell lines by MTT assay. Antimicrobial activity was tested on Gram-negative and Gram-positive bacteria using the disc diffusion method. Based on LC-MS/QTOF analysis, 430 compounds were found. The identified major compounds consist of amino acids, polyphenols, steroids, terpenoids and heterocyclic compounds which possibly act as reducing agents. 1 mM, 5 mM and 10 mM of silver nitrate solution were mixed with the leaf extract to form silver nanoparticles. 1.2 mg/ml of MP-AgNPs were found to have antibacterial activity against B. subtilis, S. aureus, E. coli, and P. aeruginosa with inhibitory zones of 8.0 ± 0.36 mm, 8.5 ± 0.45 mm, 7.5 ± 0.36 mm, and 9.0 ± 0.40 mm respectively. MP-AgNPs showed no cytotoxic activity against Caco-2 and MCF-7 cells. In conclusion, the presence of major amine compounds such as 10,11-dihydro-10,11-dihydroxyprotriptyline and harderoporphyrin in the extract facilitated the synthesis of AgNPs and the nanoparticle showed weak bioactivities in the assay conducted.

Profiling the Antidiabetic Potential of Compounds Identified from Fractionated Extracts of Entada africana toward Glucokinase Stimulation: Computational Insight.

Glucokinase plays an important role in regulating the blood glucose level and serves as an essential therapeutic target in type 2 diabetes management. Entada africana is a medicinal plant and highly rich source of bioactive ligands with the potency to develop new target drugs for glucokinase such as diabetes and obesity. Therefore, the study explored a computational approach to predict identified compounds from Entada africana following its intermolecular interactions with the allosteric binding site of the enzymes. We retrieved the three-dimensional (3D) crystal structure of glucokinase (PDB ID: 4L3Q) from the online protein data bank and prepared it using the Maestro 13.5, Schrödinger Suite 2022-3. The compounds identified were subjected to ADME, docking analysis, pharmacophore modeling, and molecular simulation. The results show the binding potential of the identified ligands to the amino acid residues, thereby suggesting an interaction of the amino acids with the ligand at the binding site of the glucokinase activator through conventional chemical bonds such as hydrogen bonds and hydrophobic interactions. The compatibility of the molecules was highly observed when compared with the standard ligand, thereby leading to structural and functional changes. Therefore, the bioactive components from Entada africana could be a good driver of glucokinase, thereby paving the way for the discovery of therapeutic drugs for the treatment of diabetes and its related complications.

Synthesis and Characterization of Ciprofloxacin Loaded Star-Shaped Polycaprolactone-Polyethylene Glycol Hydrogels for Oral Delivery.

The administration of poorly water-soluble drugs represents a relevant problem due to the low body fluids transport efficiency through hydrophilic hydrogels. Star-shaped co-polymers, i.e., amphiphilic polymers such as those with a hydrophobic core and a hydrophilic outer shell, can be used to improve weak interactions with drugs, with relevant benefits in terms of administration and controlled delivery. In this work, two different co-polymers, four-arm star-shaped PCL-PEG and six-arm star-shaped PCL-PEG, were synthesized via ring-opening polymerization to be loaded with ciprofloxacin. 1H-NMR and FTIR analyses confirmed that PCL arms were successfully grafted to the mPEG backbone, while DSC analysis indicated similar crystallinity and melting point, ranging from 56 to 60 °C, independent of the different co-polymer architecture. Therefore, both star-shaped PCL-PEGs were investigated as cargo device for ciprofloxacin. No significant differences were observed in terms of drug entrapment efficiency (>95%) and drug release, characterized by a pronounced burst followed by a slow sustained release, only slightly affected by the co-polymer architecture. This result was also confirmed with curve fitting via the Korsmeyer-Peppas model. Lastly, good antibacterial properties and biocompatibility exhibited in both star-shaped PCL-PEG co-polymers suggest a promising use for oral delivery applications.

Emergence of mRNA vaccines in the management of cancer.

INTRODUCTION: mRNA vaccines have been developed as a promising cancer management. It is noted that specification of the antigen sequence of the target antigen is necessary for the design and manufacture of an mRNA vaccine. AREAS COVERED: The steps involved in preparing the mRNA-based cancer vaccines are isolation of the mRNA cancer from the target protein using the nucleic acid RNA-based vaccine, sequence construction to prepare the DNA template, in vitro transcription for protein translation from DNA into mRNA strand, 5' cap addition and poly(A) tailing to stabilize and protect the mRNA from degradation and purification process to remove contaminants produced during preparation. EXPERT OPINION: Lipid nanoparticles, lipid/protamine/mRNA nanoparticles, and cell-penetrating peptides have been used to formulate mRNA vaccine and to ensure vaccine stability and delivery to the target site. Delivery of the vaccine to the target site will trigger adaptive and innate immune responses. Two predominant factors of the development of mRNA-based cancer vaccines are intrinsic influence and external influence. In addition, research relating to the dosage, route of administration, and cancer antigen types have been observed to positively impact the development of mRNA vaccine.

PEGylated liposomes enhance the effect of cytotoxic drug: A review.

Cancer is a second leading disease-causing death worldwide that will continuously grow as much as 70% in the next 20 years. Chemotherapy is still becoming a choice for cancer treatment despite its severity of side effects and low success rate due to ineffective delivery of the chemodrugs. Since it was introduced in 1960, significant progress has been achieved in the use of liposomes in drug delivery. The study aims to review relevant literatures on role of PEGylated liposome in enhancing cytotoxic activity of several agents. A systematic literature on the use of PEGylated liposomes in anticancer research via Scopus, Google scholar and PubMed databases was conducted for studies published from 2000 to 2022. A total of 15 articles were selected and reviewed from 312 articles identified covering a variety of anticancer treatments by using PEGylated liposomes. PEGylated liposome which is purposed to achieve steric equilibrium is one of enhanced strategies to deliver anticancer drugs. It has been shown that some improvement of delivery and protection form a harsh gastric environment of several anticancer drugs when they are formulated in a PEGylated liposome. One of the successful drugs that has been clinically used is Doxil®, followed by some other drugs in the pipeline Various drugs (compounds) had been used to enhance the efficacy of PEGylated liposomes for targeted cancer cells in vitro and in vivo. In conclusion, PEGylated liposomes enhance drug activities and have great potential to become efficient anticancer delivery to follow Doxil® in the clinical setting.

Computational and Preclinical Prediction of the Antimicrobial Properties of an Agent Isolated from Monodora myristica: A Novel DNA Gyrase Inhibitor.

The African nutmeg (Monodora myristica) is a medically useful plant. We, herein, aimed to critically examine whether bioactive compounds identified in the extracted oil of Monodora myristica could act as antimicrobial agents. To this end, we employed the Schrödinger platform as the computational tool to screen bioactive compounds identified in the oil of Monodora myristica. Our lead compound displayed the highest potency when compared with levofloxacin based on its binding affinity. The hit molecule was further subjected to an Absorption, Distribution, Metabolism, Excretion (ADME) prediction, and a Molecular Dynamics (MD) simulation was carried out on molecules with PubChem IDs 529885 and 175002 and on three standards (levofloxacin, cephalexin, and novobiocin). The MD analysis results demonstrated that two molecules are highly compact when compared to the native protein; thereby, this suggests that they could affect the protein on a structural and a functional level. The employed computational approach demonstrates that conformational changes occur in DNA gyrase after the binding of inhibitors; thereby, this resulted in structural and functional changes. These findings expand our knowledge on the inhibition of bacterial DNA gyrase and could pave the way for the discovery of new drugs for the treatment of multi-resistant bacterial infections.

Enantioselective dihydroxylation of xanthorrhizol from Curcuma xanthorrhiza via biotransformation using Aspergillus Niger.

Biotransformation is acknowledged as one of the green chemistry methods to synthesis various analogues for further valorization of natural product compounds chemistry and bioactivities. It has huge advantage over chemical synthesis due to its cost-efficiency and higher selectivity. In this work, a xanthorrhizol derivatives, namely (7 R,10S)-10,11-dihydro-10,11-dihydroxyxanthorrhizol was produced in 60% yield from the biotransformation process utilizing A. niger. The structure of the compound was established by extensive spectroscopic methods and comparison with literature data. This biotransformation successfully afforded enantioselective dihydroxylation reaction via green chemistry route. This is the first report on both biotransformation of xanthorrhizol and utilization of A. niger as its biocatalyst.

Optimisation of Vitamin B12 Extraction from Green Edible Seaweed (Ulva lactuca) by Applying the Central Composite Design.

Vitamin B12, only found naturally in animal-based foods, is essential for brain functions and various chemical reactions in the human body. Insufficient vitamin B12 leads to vitamin B12 deficiency, common among strict vegetarians due to their limited intake of animal-based foods. Nevertheless, extensive studies have demonstrated that macroalgae, specifically the Ulva lactuca species, are rich in vitamin B12 and could be further exploited in future dietary applications. In the current study, the ideal extraction method of vitamin B12 from dried U. lactuca was developed and optimised to achieve the maximum vitamin B12 yield. The effects of several extraction parameters, including the solvent-to-solvent, methanol:water (MeOH:H2O), and solute-to-solvent ratios, and pH on the total vitamin B12 content were analysed through a two-level factorial and central composite design. The highest vitamin B12 content, particularly cyanocobalamin (CN-Cbl), was recovered through the ultrasonic-assisted extraction (UAE) of oven-dried U. lactuca at 3 g:60 mL of solute-to-solvent and 25:75% of MeOH to H2O ratios at pH 4. The extraction of CN-Cbl from oven-dried U. lactuca that employed the UAE method has elevated CN-Cbl content recovery compared to other extraction methods.

Traditional Uses, Phytochemistry and Biological Activities of Alocasia Species: A Systematic Review.

The genus Alocasia (Schott) G. Don consists of 113 species distributed across Asia, Southeast Asia, and Australia. Alocasia plants grow in tropical and subtropical forests with humid lowlands. Featuring their large green heart-shaped or arrow-shaped ear leaves and occasionally red-orange fruit, they are very popular ornamental plants and are widely used as traditional medicines to treat various diseases such as jaundice, snake bite, boils, and diabetes. This manuscript critically analysed the distribution, traditional uses, and phytochemical contents of 96 species of Alocasia. The numerous biological activities of Alocasia species were also presented, which include anti-cancer, antidiabetic and antihyperglycaemic, antioxidant, antidiarrhoea, antimicrobial and antifungal, antiparasitic (antiprotozoal and anthelminthic), antinociceptive and anti-inflammatory, brine shrimp lethality, hepatoprotective, anti-hemagglutinin, anti-constipation and diuretic, and radioprotective activities as well as acute toxicity studies. Research articles were acquired by the accessing three scientific databases comprising PubMed, Scopus, and Google Scholar. For this review, specific information was obtained using the general search term "Alocasia", followed by the "plant species names" and "phytochemical" or "bioactivity" or "pharmacological activity". The accepted authority of the plant species was referred from theplantlist.org. Scientific studies have revealed that the genus is mainly scattered throughout Asia. It has broad traditional benefits, which have been associated with various biological properties such as cytotoxic, antihyperglycaemic, antimicrobial, and anti-inflammatory. Alocasia species exhibit diverse biological activities that are very useful for medical treatment. The genus Alocasia was reported to be able to produce a strong and high-quality anti-cancer compound, namely alocasgenoside B, although information on this compound is currently limited. Therefore, it is strongly recommended to further explore the relevant use of natural compounds present in the genus Alocasia, particularly as an anti-cancer agent. With only a few Alocasia species that have been scientifically studied so far, more attention and effort is required to establish the link between traditional uses, active compounds, and pharmacological activities of various species of this genus.

Natural Products-Based Metallic Nanoparticles as Antimicrobial Agents.

Natural products offer a wide range of bioactivity including antimicrobial properties. There are many reports showing the antimicrobial activities of phytochem icals from plants. However, the bioactivity is limited due to multidrug resistant properties of the microorganism and different composition of cell membrane. The antibacterial activity of the natural products is different toward Gram-negative and Gram-positive bacteria. These phenomena are caused by improper physicochemical conditions of the substance which hinder the phytochemical bioactivity against the broad range of bacteria. One of the strategies to improve the antimicrobial action is by biogenic synthesis via redox balance of the antimicrobial active substance with metal to form nanosized materials or nanoparticles (NPs). Antibiotic resistance is not relevant to NPs because the action of NPs is via direct contact with bacterial cell walls without the need of penetration into microbial cells. The NPs that have shown their effectiveness in preventing or overcoming biofilm formation such as silver-based nanoparticles (AgNPs), gold-based nanoparticles (AuNPs), platinum-based nanoparticles (PtNPs) and Zinc oxide-based nanoparticles (ZnONPs). Due to its considerably simple synthesis procedure has encouraged researchers to explore antimicrobial potency of metallic nanoparticles. Those metallic nanoparticles remarkably express synergistic effects against the microorganisms tested by affecting bacterial redox balance, thus disrupting their homeostasis. In this paper, we discuss the type of metallic nanoparticle which have been used to improve the antimicrobial activity of plant extract/constituents, preparation or synthesis process and characterisation of the plant-based metallic nanoparticles.

Biotransformation of sesquiterpenoids: a recent insight.

Sesquiterpenoids have been identified as natural compounds showing remarkable biological activities found in medicinal plants. There is great interest in developing methods to obtain sesquiterpenoids derivatives and biotransformation is one of the alternative methods for structural modification of complex sesquiterpenes structures. Biotransformation is a great drug design tool offering high selectivity and green method. The present review describes a comprehensive summary of biotransformation products of sesquiterpenoids and its structural modification utilizing a variety of biocatalysts including microorganisms, plant tissue culture and enzymes. This review covers recent literatures from 2007 until 2020 and highlights the experimental conditions for each biotransformation process.

Genus Pterocarpus: A review of ethnopharmacology, phytochemistry, biological activities, and clinical evidence.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Pterocarpus (Fabaceae) has about 46 species that are distributed over Asia, especially Indonesia, Africa, and several countries in America. Particularly, P. indicus and P. santalinus have been recorded as ancestor recipe in the old Indonesian book (Cabe puyang warisan nenek moyang). These plants have found application in traditional medicine, such as in the treatment of inflammatory diseases, gonorrhoea, infection, coughs, mouth ulcers, boils, diarrhoea, as well as in the management of pain (as an analgesic). AIM OF THE REVIEW: The present review aimed to comprehensively summarise the current researches on the traditional and scientific applications of the genus Pterocarpus with regard to the phytochemical content, in vivo and in vitro bioactivities, as well as clinical evidence that may be useful for future drug development. MATERIALS AND METHODS: Information about the Pterocarpus genus were obtained from local classic herbal literature and electronic databases, such as PubMed, Scopus, and Google Scholar. The scientific name of the species and its synonyms were checked with the information of The Plant List. Additionally, clinical trial results were obtained from the Cochrane library. RESULTS: Several phytochemical constituents of the plants, e.g., flavonoids, isoflavonoids, terpenoids, phenolic acids, and fatty acids have been reported. There are about 11 species of Pterocarpus that have been scientifically studied for their biological activities, including anti-inflammatory, anti-microbial, analgesic, and anti-hyperglycemic. Of which, the anti-hyperglycemic activity of the extracts and phytochemicals of P. indicus and P. marsupium is particularly remarkable, allowing them to be further studied under clinical trial. CONCLUSION: The present review has provided an insight into the traditional applications of the plants and some of them have been validated by scientific evidence, particularly their applications as anti-inflammatory and anti-microbial agents. In addition, the genus has demonstrated notable anti-diabetic activity in various clinical trials.

Drugs intervention study in COVID-19 management.

By 9 February 2021, the Coronavirus has killed 2,336,650 people worldwide and it has been predicted that this number continues to increase in year 2021. The study aimed to identify therapeutic approaches and drugs that can potentially be used as interventions in Coronavirus 2019 (COVID-19) management. A systematic scoping review was conducted. Articles reporting clinical evidence of therapeutic management of COVID-19 were selected from three different research databases (Google Scholar, PubMed, and Science Direct). From the database search, 31 articles were selected based on the study inclusion and exclusion criteria. This review paper showed that remdesivir and ivermectin significantly reduced viral ribonucleic acid (RNA) activity. On the other hand, convalescent plasma (CP) significantly improved COVID-19 clinical symptoms. Additionally, the use of corticosteroid increased survival rates in COVID-19 patients with acute respiratory distress syndrome (ARDS). Findings also indicated that both hydroxychloroquine and favipiravir were effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, lopinavir-ritonavir combination was not effective against COVID-19. Finally, ribavirin, galidesivir, and sofosbuvir showed potential therapeutic benefit in treating COVID-19, but there is a lack of clinical evidence on their effectiveness against SARS-CoV-2. Remdesivir, ivermectin, favipiravir, hydroxychloroquine, dexamethasone, methylprednisolone, and CP are the therapeutic agents that can potentially be used in COVID-19 management.

A new xanthone dimer and cytotoxicity from the stem bark of Calophyllum canum.

A phytochemical investigation of the stem bark of Calophyllum canum resulted in the isolation of a new xanthone dimer identified as biscaloxanthone (1), together with four compounds; trapezifoliaxanthone (2), trapezifolixanthone A (3), taraxerone (4) and taraxerol (5). The structures of these compounds were determined via spectroscopic methods of IR, UV, MS and NMR (1D and 2D). The cytotoxicity of compounds 1-3 were screened against A549, MCF-7, C33A and 3T3L1 cell lines, wherein weak cytotoxic activities were observed (IC50 > 50 µm).

Phytochemistry, Traditional Use and Pharmacological Activity of Picrasma quassioides: A Critical Reviews.

Picrasma quassioides is a member of the Simaroubaceae family commonly grown in the regions of Asia, the Himalayas, and India and has been used as a traditional herbal medicine to treat various illnesses such as fever, gastric discomfort, and pediculosis. This study aims to critically review the presence of phytochemicals in P. quassioides and correlate their pharmacological activities with the significance of its use as traditional medicine. Data were collected by reviewing numerous scientific articles from several journal databases on the pharmacological activities of P. quassioides using certain keywords. As a result, approximately 94 phytochemicals extracted from P. quassioides were found to be associated with quassinoids, ß-carbolines and canthinones. These molecules exhibited various pharmacological benefits such as anti-inflammatory, antioxidant, anti-cancer, anti-microbial, and anti-parasitic activities which help to treat different diseases. However, P. quassioides were also found to have several toxicity effects in high doses, although the evidence regarding these effects is limited in proving its safe use and efficacy as herbal medicine. Accordingly, while it can be concluded that P. quassioides may have many potential pharmacological benefits with more phytochemistry discoveries, further research is required to determine its real value in terms of quality, safety, and efficacy of use.

Genus Ophiorrhiza: A Review of Its Distribution, Traditional Uses, Phytochemistry, Biological Activities and Propagation.

Almost 50 species of Ophiorrhiza plants were reviewed in this work and the main objective is to critically analyse their distribution, phytochemical content, biological activity, and propagation. Moreover, the information would be useful in promoting the relevant uses of the plant, especially in the medicinal fields based on in vitro and in vivo studies. To this end, scientific sources, including theses, PubMed, Google Scholar, International Islamic University Malaysia IIUM EBSCO, PubChem, and Elsevier, were accessed for publications regarding the Ophiorrhiza genus in this review. Scientific literature regarding the Ophiorrhiza plants revealed their wide distribution across Asia and the neighbouring countries, whereby they were utilised as traditional medicine to treat various diseases. In particular, various active compounds, such as alkaloids, flavonoids, and terpenoids, were reported in the plant. Furthermore, the Ophiorrhiza species showed highly diverse biological activities, such as anti-cancer, antiviral, antimicrobial, and more. The genus propagation reported could produce a high quality and quantity of potent anticancer compound, namely camptothecin (CPT). Hence, it is believed that the relevant uses of natural compounds present in the plants can replace the existing crop of synthetic anticancer drugs associated with a multitude of unbearable side effects. Additionally, more future studies on the Ophiorrhiza species should be undertaken to establish the links between its traditional uses, active compounds, and pharmacological activities reported.

Pharmacological properties of Centella asiatica hydrogel in accelerating wound healing in rabbits.

BACKGROUND: Various extracts of Centella asiatica (Apiaceae) and its active constituent, asiaticoside, have been reported to possess wound healing property when assessed using various in vivo and in vitro models. In an attempt to develop a formulation with accelerated wound healing effect, the present study was performed to examine in vivo efficacy of asiaticoside-rich hydrogel formulation in rabbits. METHODS: Asiaticoside-rich fraction was prepared from C. asiatica aerial part and then incorporated into polyvinyl alcohol/polyethylene glycol (PVA/PEG) hydrogel. The hydrogel was subjected to wound healing investigation using the in vivo incision model. RESULTS: The results obtained demonstrated that: i) the hydrogel formulation did not cause any signs of irritation on the rabbits' skin and; ii) enhanced wound healing 15% faster than the commercial cream and > 40% faster than the untreated wounds. The skin healing process was seen in all wounds marked by formation of a thick epithelial layer, keratin, and moderate formation of granulation tissues, fibroblasts and collagen with no fibrinoid necrosis detected. CONCLUSION: The asiaticoside-rich hydrogel developed using the freeze-thaw method was effective in accelerating wound healing in rabbits.

Phytochemical constituents and pharmacological properties of Garcinia xanthochymus- a review.

The purpose of this study was to determine the phytochemical constituents and pharmacological properties of Garcinia xanthochymus which is commonly known as gamboge, yellow mangosteen and false mangosteen. The phytochemicals constituents, pharmacological benefits and their mechanisms were previously presented in a number of studies including in vitro and in vivo studies from published books, journals and articles. The literature used in this review were published between 1970 and 2017 and were available from databases such as Google Scholar, ScienceDirect, Scopus, PubMed, ProQuest and others. The chemical structures in this paper are drawn using ChemBio Ultra 14.0. G. xanthocymus contains many phytochemicals that can be extracted from its constituent parts; the bark, fruits, leaves, roots, twigs and seeds. The predominant extracted phytochemicals are xanthones, benzophenones, flavonoids, depsidones and isocoumarins. These phytochemicals contribute to the pharmacological activities of this plant as an antioxidant, antidiabetic, and for having Nerve Growth Factor-potentiating, antimicrobial and cytotoxic activities. This species contains a broad range of phytochemicals with curative properties that can be greatly beneficial to man. Notably, this review focused on those studies of the pharmacological effects of this plant that were concentrated on by previous researchers. Thus, further study needs to be done on G. xanthocymus in order to unlock additional potential activities and to pinpoint the exact mechanisms of how these activities can be induced, leading to new drug discoveries which have fewer side effects.