
Corn (Zea mays Linnaeus), also known as maize, is a member of the family Poaceae or Gramineae. It is indigenous to Mesoamerica and was domesticated in Mexico some 9,000 years ago, then it spread throughout the American continents [22]. Now, it is widely cultivated all over the World. The native corn includes 10,000 species, grouped in 600–700 different genera and this family includes wheat, oats, barley and rice [23]. All parts of corn are utilized, including the silks. The flowers of corn are monoecious in which the male and female flowers are located in different inflorescences on the same stalk [24]. The male flowers (tassel) at the top of the plant produce yellow pollen. Meanwhile, the female flowers produce CS and are situated in the leaf axils. The silks are elongated stigmas which look like a tuft of hairs. The colors of the CS, at first are usually light green and later turn into red, yellow or light brown. The function of CS is to trap the pollen for pollination. Each silk may be pollinated to produce one kernel of corn. The CS can be 30 cm long or longer with a faintly sweetish taste. For medicinal purpose CS is harvested just before pollination occurs and can be used in fresh or dried form.
- Phytochemical Composition
The compositions of CS extracts are important to determine their biological activities which are mainly due to their flavonoids content. Flavonoids are a widely distributed group of plant phenolic compounds which are effective as antioxidants [25]. A recent study showed that the total flavonoids (TFC) content of the butanol fraction of CS extract is in good correlation with the total phenolic content (TPC) [2]. Butanol fraction of CS is significantly higher in TPC [164.1 µg Gallic Acid Equivalent (GAE)/g DCS] and TFC [69.4 µg Rutin Equivalent (RE)/g DCS]. The upper (dark brown) parts of CS had higher amount of total phenolics (180 µg GAE/g F.W.), total anthraquinones (17.22 µg/g F.W.) and total flavonoids (119.47 µg/g F.W.) than the lower parts of CS (151.33 µg GAE/g F.W., 8.61 µg/g F.W. and 101.66 µg/g F.W. respectively) [17]. A flavonoid, 3′-methoxymaysin and reduced derivatives of maysin have been isolated and identified from CS of several corn inbreeds. The compounds isolated include 2″-O-α-L-rhamnosyl-6-C-quinovosylluteolin, 2″-O-α-L-rhamnosyl-6-C-fucosylluteolin, and 2″-O-α-L-rhamnosyl-6-C-fucosyl-3′-methoxyluteolin [26]. Five other flavonoid derivatives were isolated from CS ethanol extract (80%) and identified as 2″-O-α-L-rhamnosyl-6-C-3″-deoxyglucosyl-3′-methoxyluteolin, 6,4′-dihydroxy-3′-methoxyflavone-7-O-glucosides, ax-5″-methane-3′-methoxymaysin, ax-4″-OH-3′-methoxymaysin and 7,4′-dihidroxy-3′-methoxyflavone-2″-O-α-L-rhamnosyl-6-C-fucoside (Figure 1) [27].

Besides maysin, other flavonoid compounds isolated from CS methanol extract (100%) were c-glycosylflavones [28]. Two flavones glycoside, namely isoorientin-2-2″-O-α-L-rhamnoside and 3′-methoxymaysin, were found in CS 95% ethanol extract [2]. Several studies showed maysin was associated with the biological activities of CS, including corn earworm resistance [27,28,29,30].
A total of 36 compounds were identified by gas chromatography-mass spectrometry (GC-MS) in the volatile dichloromethane extract of Egyptian CS [31]. More than 99% of the volatile compounds obtained in the extract were the terpenoids and the main constituents werecis-α-terpinol (24.22%), citronellol (16.18%), 6,11-oxidoacor-4-ene (18.06%), trans-pinocamphone (5.86%), eugenol (4.37%), neo-iso-3-thujanol (2.59%), and cis-sabinene hydrate (2.28%) (Figure 2). These compounds are widely used for perfumery and flavor purposes in many products such as soaps, household products and cosmetics. In addition, the CS also contained cinnamic derivatives, glucose, rhamnose and rich in minerals, including sodium (0.05%), potassium (15%), iron (0.0082%), zinc (0.016%) and chloride (0.25%) [12]. The proximate compositions of corn silk consists of 9.65% moisture, 3.91% ash, 0.29% crude fat, 17.6% crude protein and 40% crude fiber [32].

- Pharmacological Studies for Potential Healthcare
Healthcare is known as prevention of diseases or illnesses in human. The CS and its bioactive components provide many benefits that can be tapped as potential natural products for healthcare applications. The pharmacological studies of CS cover both in vitro and in vivo experimental models.
4.1. Antioxidant Activity
Antioxidants are used by aerobic organisms to prevent oxidation that can damage the cells during oxygen metabolism [33]. Oxidation can cause a number of diseases including atheroscleorosis, neurodegenerative disorder, cancer, diabetes, inflammatory and aging [34]. Natural antioxidants extract from fruits, teas, vegetables, cereals and medicinal plants have been investigated extensively due to their effectiveness in eliminating free radical and claimed to be less toxic than synthetic antioxidants such as butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) [35]. There are many classes of natural antioxidants and they include vitamins such as tocopherols and vitamin C; and phytochemicals such as flavonoids and phenolic acids which are common to all plant sources [36].
The latest studies have revealed the potential use of CS extracts as an important bioactive source of natural antioxidants. Five CS fractions; ethanol extract (EF), petroleum ether fraction (PF), acetic ether fraction (AF), n-butanol fraction (BF), and water fraction (WF) were investigated in in vitro antioxidant models [2]. In the study, BF fraction (100 µg/mL) showed the highest total phenolic (164.1 µg GAE/g DCS) and total flavonoids content (69.4 µg RE/g DCS). Meanwhile, BF exhibited the strongest antioxidant activity compared to other CS fractions, whereby BF at 100 µg/mL showed the highest total antioxidant (0.789) and reducing power (1.242); meanwhile for BF at 120 µg/mL, the radical scavenging activity was 72.93% and iron-chelating activity was 62.06%. These antioxidant values were comparable with vitamin C (positive control) and ethylenediaminetetraacetic acid (EDTA).
In another antioxidant study, CS ethanol extract exhibited a good reducing power at concentrations of 0.8 and 1.6 mg/mL and the results were comparable with vitamin C (p > 0.05) [14]. Hence, the extract could serve as an electron donor leading to the termination of the free radical chain reactions. Other studies have confirmed that CS ethanol extract (400 µg/mL) provided a strong antioxidant activity by inhibiting free radical scavenging activity (84%) and the β-carotene bleaching (75%) [31]. It is believed that the antioxidant activities of CS are contributed to by its polyphenol content and there is a linear correlation between Ferric Reducing/Antioxidant Power (FRAP) values and total polyphenol, tannin, proanthocyanidin and flavonoid contents [3]. The CS antioxidant properties are able to protect liposomes from Fe2+/ascorbate induced peroxidation. According to traditional practice, CS herbal drug is prepared from the immature CS. However, the antioxidant effect shown by the CS methanol extract (4 mg/sample) from the full maturity is higher (45.9% inhibition of lipid peroxidation) than for the immature CS (22.8%) [13]. Antioxidant activities of the upper part (dark brown parts, expose to the air) and lower parts (light yellow parts not expose to the air) of CS ethanolic extract were evaluated using total antioxidant capacity and DPPH assays [17]. It revealed that the upper parts were found to have highest total antioxidant capacity (2.735 mg/g GA equivalents) and highest DPPH scavenging activity (IC50 = 0.704 mg/mL). This is due to accumulation of flavonoids and other phenolic compounds to protect maize DNA from the induction of ultraviolet damage in the upper parts of CS since this upper part is exposed to the Sun more than the lower parts. Antioxidant activity of the silks of four Zea mays varities (var. intendata, indurata, everta and saccharata) was evaluated by DPPH, superoxide (SO) scavenging activity, iron chelating capacity and ferric reducing antioxidant power (FRAP) assays [37]. All ethanol (EtOH) and ethyl acetate (EtOAc) extracts exhibited low DPPH radical scavenging activity (10%–23%) at the tested concentration (500, 1,000 and 2,000 µg/mL) whereas only the EtOH extract of Z. mays var. intendata exhibited SO scavenging activity (25%) at 200 µg/mL. The highest iron chelating capacity was for EtOH extract of Z. mays var. indurata (63%) at 500, 1,000 and 2,000 µg/mL. In the FRAP test, EtOAc extract have higher activity than EtOH extract for all varieties and Z. mays intendata exhibited the highest activity for both extracts.
Ionizing radiation can cause harmful effects in biological systems resulting in the production of free radicals and reactive oxygen species (ROS) [15]. These ROS such as hydroxyl radical (·OH) and superoxide anion (O2−) have the potential to attack the major biomolecules, particularly lipids. As such, lipid peroxidation will occur; whereby the oxidation will convert polyunsaturated fatty acids to peroxides and lipid hydroperoxides, which further break down into many cytotoxic products such as malondialdehyde (MDA). Meanwhile, glutathione (GSH) serves as a protector through free-radical scavenging, as well as provides maintenance of damaged molecules by hydrogen donation, reduction of peroxide, and maintenance of protein reduced-thiols [38]. In a study using γ-radiation-induced oxidatively stressed mice, CS ethanol extract was supplemented intragastrically at 75, 150 and 300 mg/kg/day for 10 days. The extract inhibited radiation-induced damage in liver, reduced the MDA content in a dose-dependent manner from 0.04 to 0.025 µM/g prot and protected the liver from GSH depletion, while increasing red blood cells and hemoglobin in a dose-dependent manner [15]. Another study reported that flavonoids from CS (FCS) extract provided protection against oxidative stress induced by exhaustive exercise in mice [39]. The protective effect was investigated by oral gavage of FCS (100 and 400 mg/kg body wt.) for 28 days before treadmill exercise. Exhausted mice were then anesthetized to death to remove skeletal muscle tissue for MDA and antioxidant enzyme superoxide dismutase (SOD), and glutathione peroxidase (GPX) assays. The running time for FCS treated groups were significantly increased by 41.52% (100 mg/kg body wt.) and 72.32% (400 mg/kg body wt.) as compared to control group (p < 0.05).The FCS at a concentration 100mg/kg body wt. and 400 mg/kg body wt. reduced the level of MDA significantly by 26.46% and 37.91%, respectively. The results showed that FCS protects skeletal muscle from oxidative stress induced during acute exercise. The exercise enhanced the activities of antioxidative enzymes by increased the levels of SOD and GPX significantly as compared to control (p < 0.05) and provided protection against reactive oxygen species (ROS). Radiation-induced ROS is able to destroy membrane lipids of bone marrow and peripheral blood cells. Consequently, it suppresses production of blood cells, and elevates blood cell destruction, which leads to the loss of blood cell mass and reduced significantly Nrf2 expression. In the same study, CS extract treatment induced the protein expression of Nrf2 (dose-dependently) and detoxifying antioxidant enzymes such as glutathione reductase (GR) and superoxide dismutase (SOD). Nrf2 is a transcription factor that binds to the antioxidant response element in a number of target genes which encode many of these enzymes such as GR and SOD [40]. The protein products of these genes provide protection during oxidative stress. SOD is responsible for ROS metabolizing activity and is able to catalyze the desturctions of superoxide anion and hydrogen peroxide. Meanwhile, GR is responsible for keeping the balance of GSH and glutathione disulfide (GSDS). Hence, regulation of these antioxidases is important to protect against oxidative stress. These findings have proven CS’ applications as potential antioxidants and advanced therapeutic approaches to the diseases caused by oxidative damage.