Table 1.

Effects of natural products in modulating intestinal radiation toxicity as observed in preclinical and clinical studies.

Products	Radiation dose and mode of delivery	Duration and dose of natural products/supplementation	Effects in the intestine	Citation
α-tocopherol	11 Gy, segmented intestinal irradiation	Single intraluminal administration of 5mg/ml or 250 IU of vitamin E enriched food for 10 days prior to radiation exposure	Increase in crypts per circumference and increase in mucosal height was noticed	Felemovicious et al. 1995
L-α-tocopherol	10 Gy, abdominal irradiation	Intraperitoneal administration of 20mg/kg daily for 6 days	There was no significant change in intestinal fluid absorption rate, histologic or morphometric appearance in comparison to the physiologically normal control group	Empey et al. 1992
α-tocopherol	11 Gy, total body irradiation	Single subcutaneous administration of 400 mg/kg 24 hours prior to radiation exposure	Prevented apoptosis in jejunum and promoted regeneration of crypt cells	Singh et al. 2013a
γ-tocotrienol	8.5 Gy total body irradiation	Single subcutaneous administration of 400 mg/kg 24 hours prior to radiation exposure	Reduced radiation-induced intestinal injury, enhanced hematopoietic recovery and accelerated the recovery of endothelial function biomarkers	Berbee et al. 2009
	11 Gy total body irradiation	Single dose administration of 200 mg/kg 24 hours prior to radiation exposure	Anti-apoptotic gene upregulation and intestinal crypt survival was noticed	Suman et al. 2013
δ-tocotrienol	10 – 12 Gy total body irradiation	Single subcutaneous administration of 75 – 100 mg/kg 24 hours prior to radiation exposure	Protected intestinal tissue by reducing apoptotic cells and inhibited gut bacterial translocation	Li et al. 2013
Genistein	5 – 10 Gy, abdominal irradiation	Single dose administration of 200 mg/kg 24 hours prior to radiation exposure	Inhibited intestinal inflammation, apoptosis and gut bacterial translocation	Son et al. 2013
Lycopene	6 Gy, total body irradiation	5 mg/kg oral administration for 7 days via gavage	Improved oxidant/antioxidant ratio, significantly enhanced small intestine regeneration and improved monoamine levels	Sadaa et al. 2009
Ascorbic acid	5 Gy, abdominal irradiation	Daily dose of 100 mg/kg administered over 14 days	Antioxidant properties provided protection from radiation-induced intestinal injury	Kanter & Akpolat 2008
		Daily dose of 100 mg/kg administered over 18 days
Ascorbic acid	< 12 Gy, total body irradiation	Pretreated with oral 150 mg/kg/day for 3 days followed by bone marrow transplant 24 hours after irradiation	Pretreatment reduced radiation-induced DNA damage in crypt cells and prevented denudation of intestinal mucosa	Yamamoto et al. 2010
Resveratrol	8 Gy, total body irradiation	Pretreatment with 10 mg/kg/day for 10 days before and 10 days after radiation exposure	Reversed biochemical indices and histopathological changes in the intestine due to radiation-induced injury	Velioglu-Ogunc et al. 2009
	7 Gy, partial body irradiation	40 mg/kg via gavage every day for 1 day prior to radiation exposure and 5 days post-radiation exposure	Increased defensive biomarkers (SOD2) against oxidative stress, reduced apoptosis and maintained intestinal regeneration	Zhang et al. 2017
Berberine	Experiment 1: 3, 6 and 12 Gy; Experiment 2: 16 Gy, whole abdominal irradiation in both groups	Experiment 1: 20 mg/kg via intra-gastric gavage at 12 hours, 4 hours and 1 hour before irradiation Experiment 2: 20 mg/kg via intra-gastric gavage at 12 hours, 4 hours and 1 hour before irradiation and for 8 hours after irradiation until killed for examination	Pre-treatment and post-irradiation treatment with berberine increased mean survival time and attenuated intestinal injury indicated by a reduction in interleukins and cytokines and apoptotic proteins	Li et al. 2010b
	Fractionated 36 Gy dose to iliac artery lymph node areas and 46 Gy to pelvis.	300 mg oral administration thrice daily from week 3 to week 5 post-irradiation (Eighteen patients with seminomas and lymphomas received a fractionated dose of 36 Gy and 21 patients with cervical cancer received a fractionated dose of 46 Gy to the whole pelvis)	Intensity and incidence of radiation-induced acute intestinal symptoms (anorexia, nausea, vomiting, colitis, proctitis, unintentional weight loss and diarrhea) were significantly reduced	Li et al. 2010a
Curcumin	5 Gy, abdominal irradiation	100 mg/kg oral administration daily once via gastric intubation (2 treatment groups: 1. Curcumin treatment for 10 days pre- and 4 days post-irradiation for single-dose irradiation group and 2. Curcumin treatment for 14 days pre-irradiation and 4 days post- second dose of irradiation. Radiation doses were 4 days apart)	Free radical interception resulted in an increase in the number of protective mucin-producing goblet cells in the intestine	Akpolat et al. 2009
Tea extracts	12 Gy for jejunal crypt assay; 2 Gy for apoptosis assay	50 mg/kg of green tea polyphenols administered via single intra-peritoneal injection 24 hours before irradiation	Significantly increased the number of surviving crypts and decreased the number of apoptotic cells	Lee et al. 2008
Garlic	0.5 Gy, 1 Gy, 6 Gy and 10 Gy	200 mg/kg administration of diallyl sulphide (major constituent of garlic) via gavage 3 hours prior to radiation exposure	Reduced radiation-induced nuclear aberration, reduced overall colonic injury and promoted cellular proliferation in all 4 experimental groups	Baer et al. 1989
Ginkgo biloba extract	36 Gy, partial body irradiation	100 mg/kg/day via intraperitoneal injections for 5 consecutive days before radiation exposure	Biomarkers of oxidative stress were significantly reduced resulting in protection against radiation-induced dermatitis	Yirmibesoglu et al. 2012
	8 Gy, total body irradiation	50 mg/kg/day pretreatment via intraperitoneal injections for 15 days before radiation exposure	Biomarkers of oxidative stress were significantly reduced resulting in protection against radiation-induced oxidative organ injury	Sener et al. 2006
Podophyllum hexandrum extracts	10 Gy, total body irradiation	200 mg/kg pretreatment via intraperitoneal injections 2 hours before radiation exposure	Number of surviving crypts in jejunum and cellularity were increased while the number of apoptotic bodies in the crypts were reduced	Salin et al. 2001
			Biomarkers of oxidative stress were significantly reduced resulting in protection against radiation-induced oxidative organ injury	Mittal et al. 2001
	9 Gy, total body irradiation	2.5 mg/kg pretreatment via intramuscular injections 1 hour before radiation exposure	Biomarkers of oxidative stress and free radical generation were significantly reduced, as evidenced by reduced damage to villi, crypts and mucosal layers in jejunum	Dutta et al. 2015
Aloe vera	4.5 Gy, total body irradiation	1000 mg/kg aloe vera leaf extract 15 days before radiation exposure	Antioxidant effects attributed to radical scavenging properties were reported	Dadupanthi 2015
	46 – 72 Gy external beam irradiation	1 gm of 3% Aloe vera gel twice daily for 4 weeks for 20 consecutive patients with pelvic malignancies	Symptom index score improved for any two or more of the following symptoms: rectal bleeding, abdominal/rectal pain, diarrhea or fecal urgency	Sahebnasagh et al. 2017