AZADIRACHTA INDICA MEDIATED SYNTHESIS OF METALLIC NANOPARTICLES

Plants are the source of many phytoconstituent and fewer side effects. Neem (A. indica) is a quite commonly available plant and abundant in nature. A. indica, generally known as neem, is an evergreen tree belongs to family Meliaceae. It is extensively distributed in Asia, Africa, and other semi-tropical and tropical areas of the world (Ghimeray et al„ 2009b). Its leaf extract has been found to have divergent applications in several medical fields, such as drugs and medicine. It acts as antiinflammatory, antimalarial, antifungal, anti-diabetic, antibacterial, and antiviral and is particularly recommended for skin diseases (Sharma et ah, 2010; Mgbemena et ah, 2010; Maragathavalli et ah, 2012). In India, the leaves of A. indica are desiccated and used as an insect repellent in the tropical regions to keep away the mosquitoes. It has been identified for its insecticide activity against more than 400 insect pests.

A. indica leaves have also been used to treat several skin-related diseases such as psoriasis, eczema, and others (Ghimeray et ah, 2009a; Sharma et ah, 2010). Neem is composed more than 250 natural components, such as salanin, azadirachtin, valassin, meliacin, gedunin, nimbin, and several other by-products (Girish and Bhat, 2008). Quercetin and (3-sitosterol were the first-ever-purified polyphenolic flavonoids from fresh neem leaves and possessed excellent antifungal and antibacterial properties (Alzohairy, 2016). Table 3.1 summarizes the bioactive compounds present in various parts of the neem plant.

The aqueous extract of neem is capable of synthesizing a variety of NPs, for example zinc oxide, gold, silver, copper, iron/flavanones, and terpenoids present in neem, which play an imperative role in synthesizing, as well as stabilizing, NPs by capping (Banerjee et ah, 2014).

There are numerous reports on the synthesis of silver (Chand et ah, 2019; Mohanaparameswari et ah, 2019; Ramar and Ahamed, 2018), copper/copper oxide (Abhiman et ah, 2018; Ansilin et ah, 2016), zinc oxide (Sharma and Oudhia, 2016; Bhuyan et ah, 2015), iron/iron oxide (Pattanayak and Nayak, 2013; Taib et ah, 2018; Zambri et ah, 2019), gold (Thirumurugan et ah, 2010; Bindhani and Panigrahi, 2014; Shankar et ah, 2004), nickel oxide (Helan et ah, 2016), platinum (Thirumurugan et ah, 2016), and titanium dioxide (Thakur et ah, 2019) using neem leaf extract. Shankar et ah (2004), reported the biological synthesis of Au-Ag bimetallic NPs using neem leaf broth. In another study, Amrutham et ah (2020) devised a cheap, high-yielding, single-step, and novel microwave irradiation method for synthesizing palladium NPs using neemgum.

S. No	Plant Parts	Bioactive Compounds	Biological Properties	Chemical Structure	References
1	Seeds	Azadirachtin	Insecticide, Antibacterial		Schaaf et al„ 2000

S. No	Plant Parts	Bioactive Compounds	Biological Properties	Chemical Structure	References
2		Nimbidin	Anti-inflammatory, hypoglycaemic, antibacterial, antifungal		Sarsaiya et al„ 2019
3		Nimbolide	Anticancer, antibacterial, and antifungal		Sarah et al„ 2019

S. No	Plant Parts	Bioactlve Compounds	Biological Properties	Chemical Structure	References
4		Gedunin	Antifungal and antimalarial		Biswas et al.. 2002a
5		Mahmoodin	Antibacterial		Jones et al., 1994

S. No	Plant Parts	Bioactlve Compounds	Biological Properties	Chemical Structure	References
6		Azadirachtin	Antibacterial and anticancer		Khaiid et al„ 1989
7	Bark	Gallic acid	Anti-inflammatory and immunomodulatory'		Biswas et al.. 2002a

S. No	Plant Parts	Bioactive Compounds	Biological Properties	Chemical Structure	References
8		Margolone	Antibacterial		Biswas et al.. 2002b
9		Quercetin	Antioxidant activity
10	Root	Quercetin	Antioxidant		Rao et al.. 2018

S. No	Plant Parts	Bioactive Compounds	Biological Properties	Chemical Structure	References
11		Rutin	Antioxidant		Rao ct al.. 2018
12		Melicitrin	Antioxidant		Rao ct al., 2018

(Continued)

S. No	Plant Parts	Bioactive Compounds	Biological Properties	Chemical Structure	References
13	Leaf	Salannol	Pesticides and cytotoxic		Koul et al., 2004
14		Nimbinene	Skin disease		Rao et al.. 2018
15		p-Sitosterol	Antifungal

S. No	Plant Parts	Bioactive Compounds	Biological Properties	Chemical Structure	References
16		Azadirachtol	Anti-inflammatory and antibacterial		Biswas et al.. 2002a

S. No	Plant Parts	Bioactive Compounds	Biological Properties	Chemical Structure	References
17		Nimbandiol	Antihyperglycemic, antifungal, and antimutagenic		Sarah et al„ 2019
IB		p-nimolactone	Antigastric and antibacterial		Sarah et al„ 2019
19		ot-nimolactone	Anticancerous		Sarah et al„ 2019

S. No	Plant Parts	Bioactive Compounds	Biological Properties	Chemical Structure	References
20		Epoxyazadiradione	Anti-inflammatory		Alam et al.. 2012
21		Salanin	Anti-insecticidal, antihelminthic. and antibacterial		Sarsaiya et al., 2019

FIGURE 3.1 General scheme of synthesis of metal nanoparticles using plant extracts.

The general method of synthesizing metal NPs involves the preparation of the aqueous plant extract (whole-plant extract or plant-part extract; e.g. leaf, fruit, stem, root) followed by the addition of metal salt to the same. Figure 3.1 represents a generalized scheme for the synthesis of metal NPs using plant extracts.

Whole-leaf extracts are loaded with polyphenols such as flavonoids, which are powerful reducing agents for reducing inorganic salts (Park et al„ 2011); therefore, leaf extracts are preferred for the synthesis. The majority of the research on metal/ metal oxide NPs biosynthesis using A. indica reports the use of leaf extract as a reducing agent.

The most widely utilized method of green synthesis using plants generally involves the treatment of metal salts with aqueous extract and investigating various parameters such as pH, time, temperature, the concentration of respective metal salt, and plant extract (Dwivedi and Gopal, 2010).

The bio-reduction of metal salts is considered to be brought about by the flavonoids, terpenoids, or other biomolecules present in the plant extract. The size and size distribution of the metal NPs are directly related to the reducing capacity of the biocompounds present in the plant extract. A strong reducing biomolecule tends to rapidly reduce the metal ions, forming smaller NPs (Roy et al., 2019). Bioactive compounds (flavonoids, terpenoids) serve the dual purpose by bringing about the bio-reduction of metal salts and the stabilization of as-synthesized NPs by capping or surface modification. The report of the synthesis of silver NPs by Asimuddin et al. (2018) using neem leaf extract also supports the dual action of the extract. The FTIR spectra of the neem leaf extract and synthesized AgNPs depict the presence of hydroxyl, aldehyde, phenolic, and carboxylic groups, indicating the presence of strong reducing phyto-molecules, such as terpenoids, flavonoids, and polyphenols. It was further concluded that the hydroxyl groups might have possibly played a part in reducing silver ions.

In another study, Singh et al. (2020), investigated the synthesis of ZnO particles using the extract of neem leaves. The FTIR spectra of the plant extract and bio-syn- thesized ZnO NPs, suggested the involvement of functional groups such as amines, alcohols ketones, flavones, polyols, and terpenoids in synthesis and stabilization. However, the exact mechanism involved in flavonoid- or polyol-mediated bio-reduction still needs to be deciphered.