Nanotechnology is the science of manipulating and using matter on a microscopic scale. It allows for the production of new materials, particularly those for medical uses, where older methods may be restrictive. Nanotechnology should not be regarded as a single approach with limited application (Galatage et al. 2020). Because of their unique properties and the vast variety of applications, silver nanoparticles (AgNPs) have been widely studied for decades. The use of microorganisms or plant extracts to synthesize AgNPs has emerged as a viable alternative. There are several advantages to using biosynthetic techniques. They are easy to use, cost-effective, provide great yields, and are eco-friendly (Tippayawat et al. 2016). The majority of chemical approaches for synthetic nanoparticles are prohibitively expensive and involve the use of toxic, dangerous compounds that pose a variety of biological concerns. This increases the need for ecologically friendly processes to be developed using green synthesis and other biological approaches. The production of nanoparticles utilizing diverse plants and their extracts might sometimes be more advantageous than other biological synthetic processes, which need extremely complex microbial culture maintenance procedures. The physicochemical properties of AgNPs are influenced by the size, morphology, surface, and particle distribution of nanoparticles, which can be changed using various synthetic processes, reducing agents, and stabilizers (Salleh et al. 2020). Size has been the determining factor of the biological properties of AgNPs and can be adjusted according to the specific application, typically in the range of 2–100 nm. For example, the size of AgNPs for drug delivery applications must be greater than 100 nm to accommodate the number of drugs to be delivered (Patra et al. 2015). The biological activity of AgNPs is regulated by the size distribution, surface chemistry, particle shape, chemical composition, agglomeration, capping agent, particle response in media, ion release, and the reducing agents utilized during AgNP synthesis (Prakash, et al. 2017). Nanosilver has been shown to have antibacterial, fungicidal, and wound-healing effects. The low level of silver ion release from the nanoparticle surface is principally responsible for these effects. According to extensive studies, silver nanoparticles are also less harmful than silver salts of equivalent mass (Gajbhiye and Sakharwade 2016). Fungal infections are more common in immunocompromised patients, and conquering fungi-mediated disorders is a time-consuming procedure due to the limited number of antifungal medications available at the moment. As a result, developing antifungal agents that are biocompatible, non-toxic, and environmental friendly is a foreseeable and pressing demand. AgNPs performed a significant function as anti-fungal agents against many fungal-caused diseases to help solve the problem (Verma and Maheshwari 2019).
Here is an overview of nanoparticles, their types, and their applications in various domains, with a focus on the green synthesis of silver nanoparticles from Aloe vera and Thuja orientalis leaf extract and their antifungal efficacy.
Types of nanoparticles
The nanoparticles are generally classified into organic, inorganic, and carbon-based (Sharma et al. 2019). Figure 1 includes the types of nanoparticles.
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Organic nanoparticles
Dendrimers, micelles, liposomes, ferritin, etc., are all kinds of organic nanoparticles. Biodegradable and non-toxic nanoparticles like micelles and liposomes have a hollow core and are sensitive to heat and electromagnetic waves. As a consequence of their special properties, they are a perfect alternative for drug delivery. Entrapped medication or adsorbable medication systems verify their field of application and their potency except for their traditional characteristics, like size, composition, surface morphology, and alternative such traditional characteristics. Drug delivery systems involving organic nanoparticles are widely utilized in the medical field as a result of which they operate well and might be injected into specific components of the body; this can be called targeted drug delivery (Sharma et al. 2019).
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Inorganic nanoparticles
Inorganic nanoparticles are particles that are not made from carbon. Metal and metal oxide-based nanoparticles are generally categorized as inorganic nanoparticles (Sharma et al. 2019).
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Metal-based nanoparticles
Metal-based nanoparticles are made by reducing metals to nanometric sizes using destructive or constructive methods. Metal nanoparticles are produced from the majority of metals. The unremarkably used metals for nanoparticle synthesis are aluminum (Al), cadmium (Cd), cobalt (Co), copper (Cu), gold (Au), iron (Fe), lead (Pb), silver (Ag), and zinc (Zn). Surface characteristics like high surface-area-to-volume magnitude relation, pore size, and surface charge density differentiate nanoparticles from alternative materials. Crystalline and amorphous structures distinguish nanoparticles from alternative materials. For starters, gold and silver nanoparticles, which have superior material properties and practical skills, are gaining the right smart attention from researchers. Inorganic particles are being studied due to their size and their benefits over chemical agents and medicines currently in the market for chemical imaging, as well as potential tools for disease treatment. Inorganic non-materials are widely used for cellular delivery due to their versatile choices like wide convenience, moneyed usefulness, wise compatibility, and additionally the flexibility of targeted drug delivery and controlled release of drugs (Sharma et al. 2019).
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Metal-oxide-based nanoparticles:
A good example would be iron (Fe) nanoparticles that oxidize directly to iron compound (Fe2O3) in the presence of oxygen at room temperature, which will increase their reactivity. Since metal compound nanoparticles have additionally accumulated reactivity and potency, they are synthesized in huge amounts. Aluminum oxide (Al2O3), cerium oxide (CeO2), iron oxide (Fe2O3), magnetite (Fe3O4), silicon dioxide (SiO2), titanium oxide (TiO2), zinc oxide (ZnO) are the foremost unremarkably synthesized materials. As compared to their counter components, these nanoparticles have outstanding characteristics (Sharma et al. 2019).
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Carbon-based nanoparticles
Carbon-based nanoparticles are those created entirely of carbon. Fullerenes, graphene, carbon nanotubes (CNTs), carbon nanofibers, and carbon black and sometimes activated carbon are a number of the categories of carbon nanomaterials that will be classified (Sharma et al. 2019).
Use of AgNPs for pharmaceutical active ingredients
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The chemical method of synthesizing rifampicin-conjugated silver nanoparticles (Rif-Ag) has been successfully achieved (Farooq et al. 2019).
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Antifungal drug amphotericin B was used during the AgNP's synthesis as a capping and reducing agent, resulting in AmB-AgNP’s antifungal properties (Tutaj et al. 2016).
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Silver nanoparticles with capped Solanum trilobatum extract have high antimicrobial activity after being synthesized in an eco-friendly way (Ramanathan et al. 2018).
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Synthesis of silver nanoparticles from Cassia auriculata extracts to prepare bactericidal cold cream against clinical pathogens (Sahana et al. 2014).
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Discs made from poly(methyl methacrylate) [PMMA] and PMMA nanoparticles were synthesized, while control discs used commercial acrylic resin "Nature-Cryl" (Acosta-Torres et al. 2012).
Disadvantages of silver nanoparticles
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Despite the potential of nanodrugs, safety worries are growing. The toxicity of nanodrugs is not completely understood, but researchers are working to improve their understanding. The use of nanoparticles is thought to reduce the toxicity of chemotherapeutic medications and other drugs with narrow therapeutic indexes; however, in vitro and in vivo studies have shown that some nanoparticles are cytotoxic and cause allergies or inflammation in biological systems (Ai et al. 2011).
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Inhalation of AgNPs has been linked to asthma, bronchitis, emphysema, lung cancer, and neurological illnesses. The gastrointestinal tract is also involved in Crohn's disease and colon cancer (Buzea et al. 2007)
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Several autoimmune illnesses, including systemic lupus erythematosus, scleroderma, and rheumatoid arthritis, have been linked to AgNPs that reach the circulatory system (Buzea et al. 2007)
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AgNPs are thought to be particularly hazardous to humans due to their potential toxicity. Skin that has been exposed to AgNP develops a bluish tone. Biological toxicity has been studied in other research as well, such as oxidative damage (McShan et al. 2014)
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Nanoparticles produce reactive oxygen species (ROS) and free radicals that cause oxidative stress, inflammation, DNA damage, multiple nucleate development, and fibrosis (Vega-Villa et al. 2008)
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Argyria, an irreversible discoloration of the skin and eyes caused by excessive silver deposition, has hindered the use of silver as an antibacterial agent due to its potential harmful consequences (Voorde et al. 2005)
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AgNPs also damage cells, causing DNA damage, activation of antioxidant enzymes, depletion of antioxidant molecules (e.g., glutathione), binding and disabling of proteins, and damage to the cell membrane (McShan et al. 2014)
Various strategies for synthesis of silver nanoparticles
In addition to physical, chemical, and biological strategies, green synthesis is additionally used to synthesize AgNPs. Figure 2 shows the fundamental realistic diagram of the AgNPs synthesis outline. Top-down" and "bottom-up" AgNP syntheses are the two most frequent techniques. Mechanical grinding of silver bulk may be a top-down methodology. Bottom-up strategies involve chemical reduction, sonodecomposition, and electrochemical methods (Slepička et al. 2020).
Bottom-up and top-down strategies are employed to synthesize nanoparticles. Figure 3 depicts the top-down and bottom-up approaches for the synthesis of nanoparticles. The bottom-up process involves the atom-by-atom construction of nanostructures (like a molecule) and the precipitation or condensation of product material dissolved in solvents, as well as the subsequent separation of undesirable solvents. The top-down strategy is based on reducing the size of larger particles using equipment designed to remove material from the "bulk" to build nanoscale structures (Slepička et al. 2020).
Advantages of green synthesis over chemical synthesis of silver nanoparticles (Moosa et al. 2015)
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Using this method is environmental friendly
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Cost-effectiveness is a major advantage.
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Huge synthesis may be feasible with these emerging technologies.
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You do not need to use high-pressure, high-energy, high-temperatures, or toxic materials.
Nano-based drug delivery systems
The inclusion of nanosized particles in cosmetic formulations may increase the stability of active substances including vitamins, unsaturated fatty acids, and antioxidants, hence enhancing their therapeutic potential (Pithawala and Jain 2021). Researchers are particularly interested in metallic nanoparticles because of their potential use in medicine, cosmetics, food, paint, and the textile industry (Legaspi and Fundador 2020). Despite the advantages, pharmaceutical companies are hesitant to invest more in natural product-based drug development and drug delivery systems, preferring instead to search existing chemical compound libraries for new treatments. Natural drugs have specific advantages such as reduced toxicity and adverse effects, low cost, and significant therapeutic potential. In vivo instability, limited bioavailability and solubility, poor absorption in the body, challenges with target-specific delivery and tonic effectiveness, and potential adverse pharmacological effects all complicate the use of large-sized materials in drug administration. By implementing novel drug delivery systems that target treatments to specific body locations, it might be possible to address these critical concerns the act of releasing or delivering drugs (Patra et al. 2018).
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Transdermal drug delivery system: The primary purpose of delivery systems is to reach and often pass through the organ of interest. Scientists have recently developed a slew of nanocarriers to aid in medicine delivery into the skin and across biological membranes (Escobar-Chávez et al. 2012). A transdermal medication delivery device permits a controlled release of a confined substance into the systemic circulation by permeation through skin layers. These systems are simple to install and uninstall as needed. In transdermal medication administration, the use of herbal penetration enhancers that penetrate human skin and reduce barrier resistance is generally accepted. Aloe vera (Aloe barbadensis Miller) gel, for example, has been found to improve the penetration of certain medication molecules through epidermal membranes. The physical look of transdermal films is part of their characteristics (color, clarity, completeness, uniformity, surface texture, and flexibility). The film's thickness, folding endurance, flatness studies, weight fluctuation, moisture content, percentage moisture uptake hardness, tensile strength, and percent elongation of the substance of the drug, stability research, in vitro drug release studies, in vitro drug release research, and in vitro skin permeation studies are all examples of in vitro drug release studies (Sharma 2016).
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Cream: To address diverse skin diseases and infections, novel dermatological and cosmetic formulations with antibacterial and antifungal properties are used (Sonia et al. 2017). Topical medications that can be applied to the skin are known as creams. Creams are “viscous liquid or semi-solid emulsions of either the oil-in-water or water-in-oil type,” according to the definition. The consistency of the dose forms differs depending on whether they are made of oil or water. These topical formulations are used to transfer drugs into the underlying layer of the skin or the mucous membrane for a localized effect. For skin disorders, a specialized drug administration into the skin is required (Chauhan and Gupta 2020). Creams can be ayurvedic, herbal, or allopathic which are used by people according to their needs for their skin conditions. They contain one or more drugs substances dissolved or dispersed in a suitable base. Creams may be classified as o/w or w/o type of emulsion based on phases (Sahu et al. 2016). The assessment of silver nanoparticle-incorporated cream involves physicochemical attributes that include grittiness, pH, and rheological property, emulsion, and stability tests (Pithawala and Jain 2021).
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Gel: According to the USP, gels are semisolids made up of minute inorganic particles floating in a liquid or large organic molecule interpenetrated by liquid. Gels are clear or translucent semisolid compositions with a high solvent/gelling agent ratio. In comparison with creams and ointments, gels frequently give a faster release of pharmacological material, regardless of the medication's water solubility. They are highly biocompatible, with a lesser chance of irritation or bad reactions, and they are simple to apply and remove. Thixotropic, greaseless, readily spreadable, quickly removed, emollient, non-staining, compatible with a variety of excipients, and water-soluble or miscible are only a few of the benefits of dermatological gels. Different features of the gel can be tested, including pH, spreadability, extrudability, viscosity, swelling characteristics, in vitro drug diffusion, and drug release kinetic investigations (Prusty and Parida 2014).
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Nanoemulsions: Nanoemulsions, also known as submicron emulsions, ultrafine emulsions, and mini-emulsions, are isotropic dispersions made up of two immiscible liquids, such as water and oil, stabilized by an interfacial film made up of an appropriate surfactant and co-surfactant to create a single phase (Gurpreet and Singh 2018). It does not form on its own; it requires external shear to break up bigger droplets into smaller ones (Panda et al. 2017). Two approaches for making nanoemulsions are persuasion and brute force. Various characterization approaches for nanoemulsions include entrapment efficiency, particle size, polydispersity index, zeta potential, and characterization using differential scanning calorimetry, as well as Fourier transform infrared spectroscopy and transmission electron microscopy. Furthermore, drug release, in vitro permeability, stability and thermodynamic stability, shelf life, dispersibility, and surface tension, as well as pH and osmolarity are all examined in vitro (Gurpreet and Singh 2018).
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Nanosuspension: A biphasic system consisting of pure drug particles dispersed in an aqueous vehicle with a diameter of fewer than 1 m and stabilized by surfactants, nanosuspension is a biphasic system consisting of pure drug particles dispersed in an aqueous vehicle with a diameter of fewer than 1 m and stabilized by surfactants. They can be used to increase the solubility of medications that are not well soluble either in water or fat. As a result, the rate of flooding of the active component rises, resulting in a faster reach of the maximum plasma level. Nanosuspension has several advantages over traditional suspensions, including increased dissolution velocity, drug saturation solubility, enhanced biological performance, long-term physical stability, and ease of fabrication (Panda et al. 2017).
Taxonomy and chemical constituents of Aloe vera and Thuja orientalis plant
Aloe vera:
Scientific name:
Aloe barbadensis Miller.
Synonyms: Aloe perryi Baker, Aloe vera Linn or Aloe barbadensis Mil and Aloe ferox Miller.,
Biological source: Aloe is the dried juice collected by incision, from the bases of the leaves of various species of Aloe.
Family: Liliaceae.
Chemical constituents: Aloe vera contains more than 75 different compounds, including vitamins (vitamin A, C, E, and B12), enzymes (i.e., amylase, catalase, and peroxidase), minerals (i.e., zinc, copper, selenium, and calcium), sugars (monosaccharides such as mannose-6-phosphate and polysaccharides such as glucomannans), anthraquinones (aloin and emodin), fatty acids (i.e., lupeol and campesterol), hormones (auxins and gibberellins), and others (i.e., salicylic acid, lignin, and saponins) (Sánchez et al. 2020).
Aloe vera as shown in Fig. 4 is a semi-tropical plant. Throughout history, it has been described as an all-purpose herb with notable accomplishments. The plant’s thorny, tapered leaves are held up by short shoots near the surface of the soil or soil surface. Fresh gel is usually recommended because some of the active ingredients in the gel seem to diminish over time. An adhesive-like substance forms on the skin when Aloe vera gel is applied. This acts as a natural "band-aid," keeping nutrients in and preventing bacteria or agents from prohibiting healing. Aloe vera gel also contains a significant amount of water, which is essential for the body's recovery process.
Traditional healers' uses that are not supported by experimental or clinical evidence include the treatment of skin disorders, hemorrhoids, psoriasis, anemia, glaucoma, petit lesion, tuberculosis, blindness, seborrheic eczema, and fungus infections. As well as being effective when taken orally, Aloe vera can be used topically as an ointment, cream, or lotion. Dermo therapeutic use of Aloe vera is widespread because it is an astringent, body lotion, humidifier, and cleanser. It softens the skin, lowers wrinkles, and cures acne, herpes, red spots, psoriasis, eczema, mycosis, fever blisters, skin irritation, and protects the skin from pollution. Aside from that, it is ideal for curing sunburns, fragile skin, and removing dead skin cells and skin. Most of the amino acids and vitamins that our skin needs to heal are found in Aloe vera, making it an excellent healing agent.
Herbal penetration enhancers, in particular, have received a lot of attention, and Aloe vera, an ostensibly skin-friendly and humectant product, is one such enhancement system. While there is some evidence suggesting that Aloe vera enhances skin penetration, only one paper mentions its use as a vehicle for various substances. As a result of two recent US patent filings, Aloe vera is credited with increasing the skin penetration of co-formulated treatments.
Aloe seems to increase penetration as:
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It penetrates deep into the epidermis.
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It maintains the skin's acid-alkaline pH balance.
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Bacteria, viruses, and fungi are prevented from multiplying.
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It is an anti-inflammatory and astringent, and it is also a natural preservative.
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In addition, it provides pain relief and itching relief.
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It helps to stay the skin hydrated and healthy.
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It dilates the blood vessels under the skin and speeds up the blood flow through the system.
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In addition, it promotes cell division and accelerates tissue healing.
Aloe vera contains lignin, which allows it to penetrate the cellular level and have positive benefits. This plant also contains saponin, a natural cleaner. Both of these components must work together to accomplish cellular penetration (Sharma et al. 2015).
Aloe vera is recognized to possess several medicinal properties since thousands of years ago. It contains treasures of nutritional and antipathogenic compounds. Aloe vera is opted for the synthesis of silver nanoparticles due to the presence of natural phytochemicals which offer natural capping and reducing agents. Aloe vera extracts are used for the synthesis of stable many studies that have looked at the bactericide, antifungal, and mosquitocidal properties of AgNPs. Aloe extracts contain compounds that cause steric repulsion between individuals, which prevents nanoparticles from aggregating. Using Aloe vera as a surface-active agent prevents nuclei aggregation by decreasing the overall surface energy result of it contains a large number of chemical constituents (Vélez et al. 2018).
Thuja orientalis: Thuja plant is shown in Fig. 5.
Scientific name:
Thuja orientalis.
Synonyms: Morpankhi, Oriental thuja, Oriental arborvitae, Vidya plant.
Family: Cupressaceae.
Chemical constituents: Rhodoxanthin, amentoflavone, hinokiflavone, quercetin, myricetin, carotene, xanthophylls, and ascorbic acid are all found in conifer leaves. per Nickavar et al., nineteen and twenty-eight compounds were found among the volatile oils of the fruit and leaf, severally, with the fruit oil containing—pinene (52.4%), 3-carene (14.2%), -cedrol (6.5%), and phellandrene (5.1%), and thus the leaf oil containing -pinene (21.9%), -cedrol (20.3%), 3-carene (10.5%), and hydrocarbon (7.2 Thujone may well be associated organic compound and monoterpene that comes in a pair of diastereomeric forms in nature: -thujone and -thujone (Srivastava et al. 2012).
Uses: It is used to treat bronchial inflammation, enuresis, cystitis, psoriasis, female internal reproductive organ carcinomas, amenorrhea, and rheumatism in several types of ancient medication like folk medication and homeopathy. The herb Thuja is also used to treat skin, blood, digestive system, renal, and brain diseases, as well as wart-like excrescences and spongy tumors. Various ailments such as coughs, hemorrhages, excessive menstrual flow, bronchitis, asthma, skin infections, anemia, rheumatic aches, and premature blandness are all treated with Oriental arborvitae. Hair development is assumed to be assisted by their use. Antipyretic, astringent, diuretic, emmenagogue, emollient, expectorant, refrigerant, and stomachic are all properties of the leaves (Srivastava et al. 2012).
Thuja orientalis (also known as Morpankhi) is a coniferous tree genus that belongs to the Cupressaceae family. T. Orientalis is a monoecious, evergreen tree, or shrub that reaches a height of 10–60 feet. There are five species in the genus, two of which are endemic to North America and three to eastern Asia. Vidya plant, scientific name Thuja, is a non-flowering, seed-bearing evergreen garden shrub native to India (Srivastava et al. 2012).
It is an evergreen coniferous tree used in landscaping, with a shallow cup in its early years that widens as it becomes older, a conic overall shape, and laminar branching. The branches are fan-like in appearance and are disposed of upwards. Branches and leaves are flat in shape. Every branch changes color from deep green to green yellowish color as it gets closer to the tip. It is a dioic tree, with female cones that are whitish or rose pale and later bluish-green, with well-marked tips that open like spikes, each of which is a squama and has 6–8 flattened oval form, are thick, and have an apical hook, the cone is dehiscent when mature and turns brownish-tan. Every cone contains about 6 ovoid-trigonoidas seeds and is expelled wingless. The leaves are flattened fan-shaped and have resin glands on them. Essential oils found in the leaves of these plants are used to cure fungal infections, cancer, moles, and parasitic worms (Hernández and Arenas 2016). The essential oil that is extracted from the leaves is poisonous. α-Thujone is an insecticide and antihelminthic substance that can be used to treat parasitic worms. α-Thujone, on the other hand, is a poisonous chemical that interferes with neurological signals in the brain (Sharma and Sharma 2016).