Resveratrol, 3,5,4’-trihydroxystilbene, is a kind of natural plant antitoxin, which belongs to the category of non-flavonoid polysaccharides and is also an antibiotic secreted by plants to resist fungal infection under pathogen attack. Resveratrol exhibits lipophilic characteristics which lead to high absorption, but the systemic bioavailability of resveratrol is relatively low. The plasmatic concentration of resveratrol plus total metabolites is around 400–500 ng/mL (≈2 μM) after a 25 mg oral dose [44]. An isotope tracer experiment has shown that radioactivity derived from ¹⁴C-resveratrol can be detected in various organs such as the liver, kidney, brain, heart, lung, testis, and intestine after oral intake of ¹⁴C-resveratrol. This suggests that resveratrol or its metabolites can enter almost all organs after intake [45]. Resveratrol shows a strong antioxidant ability in poultry. Sahin et al. [46] reported that quails supplemented with 400 mg/kg resveratrol had a lower serum MDA concentration (p < 0.05) and a higher serum vitamin E concentration (p < 0.05). Zhang et al. [47] revealed that supplementation of 400 mg/kg resveratrol increased muscle glycogen content and the activities of total superoxide dismutase (T-SOD) and GSH-Px (p < 0.05) but decreased muscle MDA content and lactate dehydrogenase (LDH) activity (p < 0.05) in transport stress-impaired broilers. Liu et al. [48] also reported that supplementation of 200, 400, or 600 mg/kg resveratrol efficiently attenuated heat stress in black-boned chickens, and the dose of 400 mg/kg showed the strongest antioxidant effect.

Many studies have reported that resveratrol can effectively scavenge ROS, regulate the activity of various antioxidant enzymes, reduce DNA damage, and significantly enhance the expression levels of various antioxidant enzymes and proteins. The antioxidant effect of resveratrol is stronger than that of vitamin C, and it is more effective in scavenging ·OH. Das et al. [49] reported that dietary supplementation of resveratrol can inhibit lipid peroxidation and improve enzyme (SOD, GSH-Px, CAT) activity (p < 0.05) in hepatocytes, thus relieving liver damage caused by heat stress in rats. Zhang et al. [50] also reported that resveratrol could protect against the heat stress-impaired meat quality of broilers by increasing the muscle total antioxidant capacity (T-AOC) and activity of antioxidant enzymes (CAT, GSH-PX). Our previous study revealed that resveratrol could significantly increase the average daily feed intake (ADFI) and average daily weight gain (ADG) of black-boned chickens and reduce feed to gain ratio (F/G ratio) under the condition of heat stress. This occurred as a result of the restoration of antioxidant enzyme activity that was decreased by heat stress [48,51]. Liu et al. [32] reported that resveratrol could alleviate intestinal injuries by increasing mRNA and protein expression of Hsp70, Hsp90, and NF-kappa B, and suppressing the production of epidermal growth factor (EGF) in the mucosa.

Curcumin (feruloyl methane) is a yellow polyphenol extracted from the traditional Chinese medicine, zingiber plant. Since the discovery of curcumin in 1815, it has become one of the most widely used natural pigments. Animals can easily absorb curcumin. Ravindranath et al. [52] reported that about 60% was absorbed after oral administration of 400 mg curcumin to rats. In another rat experiment conducted by Marczylo and colleagues [53], curcumin was found in the plasma (16.1 ng/mL), urine (2.0 ng/mL), intestinal mucosa (1.4 mg/g), liver (3671.8 ng/g), kidney (206.8 ng/g), and heart (807.6 ng/g) after oral intake of 340 mg/kg of curcumin. Curcumin can therefore effectively distribute to all parts of the body after intake, potentially undergo metabolic O-conjugation to curcumin glucuronide and curcumin sulfate, as well as bio-reduction to tetrahydrocurcumin, hexahydrocurcumin, octahydrocurcumin, and hexahy-drocurcuminol [54].

The 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH) and 2,2′-azino-bis (3-ethylbenzthiazoline -6-sulfonic acid) (ABTS) radical scavenging ability of curcumin is higher than that of artificial antioxidant butylated hydroxyanisole (BHA) [55]. Many studies have shown that curcumin can improve poultry’s growth performance under heat stress [56,57,58]. Curcumin can restore the impaired growth performance caused by heat stress potentially due to its capacity to mitigate the broilers’ mitochondrial dysfunction and enhance the mitochondrial biogenesis caused by heat stress. Zhang et al. [58] reported that curcumin decreased the ROS production of broilers after heat stress by increasing the mitochondrial Mn-SOD activity and gene expression of thioredoxin 2 and peroxiredoxin-3. Curcumin can also decrease the mitochondrial malondialdehyde levels and increase mitochondrial glutathione content as well as the activities of GSH-Px, glutathione S-transferase (GSST), and Mn-SOD [57].

Epigallocatechin gallate (EGCG) is the primary component of green tea extract, which possesses strong antioxidant and anti-inflammatory properties and shows higher bioavailability than other polyphenols. The absolute bioavailability of EGCG in mice is 26.5% according to Lambert et al. [59]. Epigallocatechin gallate undergoes methylation, glucuronidation, and sulfation in vivo [59], but mostly presents in free form in the plasma and can thus effectively spread around the body [60]. Suganuma et al. [61] directly administered the [H-3] (−)-epigallocatechin gallate ([H-3]EGCG) into the mouse stomach and found significant radioactivity in the digestive tract, liver, lung, pancreas, mammary gland, skin, brain, kidney, uterus ovary, and testes. Multiple studies have reported that EGCG can attenuate heat stress in poultry. Xue et al. [62] revealed that supplementation of 300 and 600 mg/kg EGCG in heat-stressed broilers could increase growth performance in a dose-dependent manner. Luo et al. [63] also reported that a supplement of 600 mg/kg EGCG in heat-stressed broilers showed the best antioxidant property. Sahin et al. [64] reported that supplement with 400 mg/kg EGCG in heat-stressed quails showed the best antioxidant property. Thus 400–600 mg/kg of EGCG may be the optimal dosage in poultry.

Supplemental EGCG can maintain the equilibrium of oxidation–reduction and improve the expression of antioxidant genes (SOD, CAT, GSH-Px), thus reducing the damage caused by oxidative stress [65]. Supplemental EGCG can improve the poultry’s growth performance and alleviate the oxidant damage under heat stress by modulating the antioxidant enzymes [62,63,64]. Epigallocatechin gallate enhances antioxidant enzyme activity mainly due to the fact that it can activate nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathways. Sahin et al. [64] reported that EGCG improves antioxidant capacity by regulating the transcription factor Nrf2 as well as Nrf2-regulated heme oxygenase -1(HO-1). However, Orhan et al. [66] reported that EGCG could also decrease hepatic expression of activator protein-1 (AP-1), cyclooxygenase-2 (COX-2), and heat shock proteins (Hsps). Thus, EGCG potentially attenuates heat stress through modulating stress-responsive transcription factors.

The beneficial effects of polyphenols as a potential attenuator of heat stress are mainly attributed to their antioxidant activities. Polyphenols can act as radical scavengers depending on their chemical structures [67] and thus scavenge ROS including O₂•⁻, •OH, and H₂O₂ to eliminate the oxidative damage caused by heat stress [68]. The phenol functional group of polyphenols can donate a hydrogen atom to the free radicals and direct quenching ROS. Also, they may block the action of some enzymes (e.g. xanthine oxidase and protein kinase C) that directly generate O₂·⁻ [69,70]. Furthermore, polyphenols can modulate cell signaling pathways to alleviate the impact of heat stress. On the one hand, resveratrol [32], EGCG [64], and curcumin [54] have been proven as potent inhibitors of nuclear factor kappa B(NF-κB), which can transcribe inflammatory markers such as interleukin-6 (IL-6), interleukin-2 (IL-2), and tumor necrosis factor α (TNF-α) to cause inflammation [71]. On the other hand, resveratrol [72], EGCG [64], and curcumin [56] may upregulate the antioxidant response pathways such as the transcription factor Nrf2 mediated antioxidant enzymes to improve the antioxidant enzyme system. Under a heat stress situation, resveratrol and EGCG can enhance the activity of antioxidant enzymes (CAT, GSH-Px, SOD) [50,51] and non-enzyme systems (GSH [51], vitamin E [46]), while curcumin can increase the activity of Mn-SOD, GSH-Px, and GSST [56]. In addition, polyphenols may attenuate heat stress by regulating the expression of heat shock proteins. Resveratrol can upregulate the transcription level of Hsp70 and Hsp90 in the immune organs of black-boned chickens under heat stress and directly participate in the immune response against the damage caused by heat stress [48]. However, EGCG has been reported to suppress the elevated hepatic expression of Hsps caused by heat stress, specifically inhibiting the expression of Hsp70 and Hsp90 by restraining the promoter activity [66]. To our knowledge, there is no direct evidence to demonstrate the mechanism of polyphenols alleviating damage caused by heat stress through the inhibition of Hsps expression.

The bioavailability of polyphenols remains controversial due to the low absorption rate since polyphenols undergo various metabolisms such as methylation, glucuronidation, and sulfation after intake [59]. Generally, the concentration of the parent structure of polyphenols rather than their metabolites were detected in early studies [73]. However, recent studies have shown that phenolic metabolites possess strong biological activities, thus the bioavailability of polyphenols should not exclude their phenolic metabolites [74]. The stomach and small intestine are the main absorption sites of polyphenols. An isotope tracer experiment with resveratrol showed that the concentration of radioactivity in the intestinal tract was the highest [45]. The concentration of curcumin in intestinal mucosa can reach 1.4 mg/g after intake of 340 mg/kg curcumin [53]. Around 33% of EGCG can be excreted in feces [60]. Therefore, the gut should be the main place for the function of polyphenols. The liver is the main metabolic organ and also a target of polyphenols. The concentration of curcumin in the liver can reach 3.6 mg/g at a dose of 340 mg/kg [53]. High concentrations of radioactivity were detected in the liver in the isotope tracer experiment with resveratrol and EGCG [45,60]. The high concentration of polyphenols in the liver can potentially explain the hepatoprotection ability under heat stress. In addition, polyphenols can also reach circulation and other organs. Plasma concentration of curcumin can reach 16.1 ng/mL at a dose of 340 mg/kg [53]. Radioactivity can be detected in the kidney, testis, lung, pancreas, skin, mammary gland, and even brain after intake of isotope labeled resveratrol and EGCG [44,61]. This may also explain why polyphenols are capable of attenuating systemic disorders caused by heat stress.