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Effects of flavonoids from Allium mongolicum Regel on growth performance and growth related hormones in meat sheep Accepted Manuscript Effects of flavonoids from Allium mongolicum Regel on growth perf[.]

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Effects of flavonoids from Allium mongolicum Regel on growth performance and

growth-related hormones in meat sheep

Muqier, Sarula Qi, Terigele Wang, Renwei Chen, Cuifang Wang, Changjin Ao

PII: S2405-6545(16)30156-1

DOI: 10.1016/j.aninu.2017.01.003

Reference: ANINU 133

To appear in: Animal Nutrition Journal

Received Date: 29 August 2016

Accepted Date: 10 January 2017

Please cite this article as: Muqier Qi S, Wang T, Chen R, Wang C, Ao C, Effects of flavonoids from

Allium mongolicum Regel on growth performance and growth-related hormones in meat sheep, Animal Nutrition Journal (2017), doi: 10.1016/j.aninu.2017.01.003.

This is a PDF file of an unedited manuscript that has been accepted for publication As a service to our customers we are providing this early version of the manuscript The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Effects of flavonoids from Allium mongolicum Regel on growth performance and

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growth-related hormones in meat sheep

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Muqier, SarulaQi, Terigele Wang, Renwei Chen, Cuifang Wang, ChangjinAo*

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College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018,

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China

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* Corresponding author

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E-mail address: changjinao@aliyun.com (C Ao)

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ABSTRACT

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This study was conducted to investigate the effects of different doses of flavonoids

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from Allium mongolicum Regel on the production performance and neuroendocrine

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hormones in meat sheep and to determine the optimum dosage of Allium mongolicum

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Regel flavonoids to add to the basal diet of dry lot-feeding meat sheep Sixty meat

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sheep (initial body weight = 39.9 ± 3.2 kg; 6-month-old) were randomly assigned to 4

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groups (15 sheep per group) The sheep in the control group were fed a basal diet, and

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the 3 experimental groups were fed the basal diet supplemented with flavonoids at 11,

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22 and 33 mg/kg Blood samples were collected via the jugular vein at d 0, 15, 30, 45,

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and 60 to determine the neuroendocrine hormone levels The fasting weight of the

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sheep was measured during the experimental period, and feed offered and refusals

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were recorded daily The basal diet supplemented with flavonoids from 11 to 33 mg/kg

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significantly increased the daily weight gain and average daily feed intake (P < 0.05)

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and significantly decreased the feed conversion ratio (P < 0.05), but there were no

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differences among the supplementation groups (P > 0.05) Starting on d 30, the growth

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hormone (GH) and insulin-like growth factor-I (IGF-I) levels in the sera of the sheep in

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the supplementation groups increased significantly (P < 0.05), and the increases

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occurred in a time-dependent manner Compared with control group, after d 30, the

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serum corticosterone (CORT) levels were reduced in the sheep that consumed the basal

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diet supplemented with 22 mg/kg flavonoids (P < 0.05), but among the other

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experimental groups, there was a non-significant effect (P > 0.05) The serum

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adrenocorticotropic hormone (ACTH) levels were increased by the supplementation of

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flavonoids, but compared with the control group, the effect was not significant The

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basal diet supplemented with flavonoids at levels of 11 to 33 mg/kg had a significant

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effect on the production performance and neuroendocrine hormone levels of meat

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sheep, and the effect occurred in a time-dependent manner The effect was especially

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obvious after 30 d of feeding

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Key words: Allium mongolicum Regel, Flavonoids, Growth performance, Hormones,

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Meat sheep

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1 Introduction

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Allium mongolicum Regel, also known as the Mongolia leek, is a type of

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Liliaceous allium plant that grows in high altitude desert steppe and desert areas; it is

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perennial and xerophytic (Wang et al., 2013) It is mainly found in desert land in

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Qinghai, Gansu, Xinjiang and Inner Mongolia, and is especially abundant in the

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western areas of Xilingol, Ordos, and Alxain Inner Mongolia Allium mongolicum

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Regel, as a characteristic wild vegetable, is a natural and healthy food with a high

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nutritional value, unique flavour and supreme palatability (Chen et al., 2000) Allium

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mongolicum Regel and its extracts have been shown to increase the average daily gain

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(ADG), feed intake and feed remuneration of broiler chickens (Ha, 2008) and to

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significantly affect growth-related hormones (Zhang, 2005)

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Flavonoids are active ingredients in natural plants that can promote growth,

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neuroendocrine and immune function of animals Related research found that the

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isoflavone daidzein promoted animal growth (Han, 1999), improved immune function

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(Guo et al., 2004), and enhanced lactation and laying (Hu and Zhang, 2009; Yang,

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2006) Flavonoids are an important active substance in Allium mongolicum Regel (Sa,

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2014a) According to research, Allium mongolicum Regel flavonoids show

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biological efficacy as anti-oxidants and have anti-bacterial and immune regulation

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abilities Allium mongolicum Regel provides small doses, low toxicity, and high

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efficacy in practical application; consequently, it offers good latent capacity for new

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types of feed additives Animal growth is a complicated metabolic process influenced

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by genes, nutrients, hormones and the environment and regulated by neuroendocrine

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function (Tao, 2006), of which the hypothalamic-pituitary-growth axis is the key

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regulator(Sarah, 2003)

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Currently, research on the flavonoids from Allium mongolicum Regel has mainly

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focused on its in vitro anti-oxidant, anti-bacterial and anti-viral activities; studies of

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growth performance and growth-related hormones in meat sheep are rare On the basis

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of a preliminary in vitro study (Bao, 2015; Sa, 2014b), this study selected the

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flavonoids from Allium mongolicum Regel as feed additives for meat sheep Different

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doses of flavonoids from Allium mongolicum Regel were added to the basal diet, and

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the effect on growth performance and growth-related hormones in meat sheepwas

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explored A suitable amount of flavonoids from Allium mongolicum Regel was

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determined for use as a natural feed additive

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2 Materials and methods

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2.1 Experimental flavonoids from Allium mongolicum Regel

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The flavonoids from Allium mongolicum Regel were extracted using the

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extraction processing method described by Saruli (Sa, 2014b) An ultrasonic extraction

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method was adopted using the following parameters: extraction time = 15 min,

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extraction temperature = 40 °C, alcohol density =75%, and material-to-liquid ratio =

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1:30 The projected total flavonoid yield was 12.85 mg/g The flavonoids from Allium

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mongolicum Regel are yellow in colour and insoluble in water According to early

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research regarding structure identification (Sa, 2014b), the structure contains

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saccharides, naphthenic hydrocarbon,3',4' -epoxygroup-7-0-5-methoxy flavonols,

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7-0-5,4'-dimethoxy-3'-hydroxide radical flavones, rutin, quercitrin, saccharides,

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mignonette element - 5 0 - glucose - 4 - hydroxybenzoic acid, and acacia

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2.2 Reagents and apparatus

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Testing kits were used to determine the levels of serum growth hormone (GH;

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HY-C0018), serum insulin-like growth factor-1 (IGF-1; HY-H0024), serum

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corticosterone (CORT; HY-D0032), and serum adrenocorticotropic hormone (ACTH;

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HY-D0023) The testing method was radioimmunoassay, and the test apparatus was an

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r-911 auto radio free counter (provided by the Science and Technology Industrial

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Company of the University of Science and Technology of China) All

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reagents and apparatuses were provided by the Beijing Sino-UK Institute of Biological

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Technology

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2.3 Experimental method

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2.3.1 Selection of experimental animals

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A total of 60 six-month-old healthy meat sheep with initial body weight of 39.9 ±

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3.2 kg were divided into 4 groups of 15 sheep, which included the control group, test

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group1, test group 2 and test group 3

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2.3.2 Experimental diet

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The control group was fed a basal diet, and the 3 test groups were supplemented

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with 11, 22, and 33 mg/kg flavonoids from Allium mongolicum Regel According to the

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stability test of flavonoids from Allium mongolicum Regel in the rumen, adding 22

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mg/kg of total flavonoids from Allium mongolicum Regel to the rumen could improve

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parameters related to rumen microbial fermentation gas production, pH, ammonia

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nitrogen, microbial protein, and volatile fatty acids and could optimize the effects of

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the flavonoids (Bao, 2015) This study referred to these previous results when choosing

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the supplementation doses (11, 22, and 33 mg/kg) of flavonoids from Allium

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mongolicum Regel The components of the experimental diet testing method (Zhang,

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2003) were as follows: 1) The crude protein of the feedstuff was tested using the

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Kjeldahl Nitrogen Determination method; 2) The Van Soest detergent fibre analysis

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method was used for the determination of neutral detergent fibre (NDF) and acid

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detergent fibre (ADF) contents; 3) The calcium content of feedstuff was tested using

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potassium permanganate titration; 4) The phosphorus content was determined using

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colorimetry with molybdenum yellow The basic dietary composition and nutritional

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levels are shown in Table 1

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2.3.3 Feeding management

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The entire experimental period lasted 75 d, and the adaptation period lasted 15d

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Parasites were expelled, and disinfection and epidemic prevention efforts were applied

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to the experimental sheep The normal experimental period was 60 d, during which

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feed was given at 06:00 and 18:00, and water was given ad libitum The ratio of the

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roughage to concentrate was 7:3 The control group was given the basal diet, and the

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test groups were given the appropriate experimental diet

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2.3.4 Sample collection and treatments

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During the experimental period, feed offered and refusals were recorded, and

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sheep was weighted before feeding at 0, 15, 30, 45, and 60 d, which were prepared to

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calculate the performance index Meanwhile, sterile blood samples from the jugular

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veins of the sheep were bottled into 5-mL tubes containing no anti-coagulant Blood

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samples were stood for 40 min, and centrifuged by an 800 × g vertical centrifuge for

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10 min After sera were separated out, samples were stored at -20 ℃ and prepared for

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hormones testing

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2.3.5 Determination index

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The following variables were measured: average daily gain (ADG), average daily

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intake, average feed conversion ratio, growth hormone (GH), insulin-like growth

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factor-I (IGF-1), corticosterone (CORT), and adrenocorticotropic (ACTH)

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2.4 Statistical analysis

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Statistical analyses were performed using the method for double-factor variance

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analysis GLM in SAS9.0 The values are given as means ± standard deviations The

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significance level of 0.05 was adopted

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3 Results

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3.1 Effect of flavonoids from Allium mongolicum Regel on growth performance

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The growth performance included average daily gain (ADG), average daily feed

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intake and feed conversion ratio

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3.1.1Average daily gain

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The results indicated the F value of experimental time was 2.97, which had an

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obvious effect on ADG (P = 0.03) The results show after 30 d of feeding, ADG

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changed significantly (P < 0.05) However the F value of the interaction effect

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between experimental time and treatment was 0.95, so there were no significant

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interaction effects between them (P = 0.48) Table 2 shows the flavonoids from Allium

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mongolicum Regel had a clear effect on ADG The ADG of the sheep that consumed

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the diet supplemented with flavonoids for 15 d showed no significant change (P > 0.05)

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compared with the control group However, after 30 d, the ADG of the 3 test groups

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showed an increasing trend, and far surpassed that of the control group (P < 0.05)

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After 45 d, the ADG in test group 3 was significantly higher than that of the control

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group (P < 0.05), but the ADG did not vary significantly among the experimental

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groups (P > 0.05) Between d 45 and 60, the flavonoids from Allium mongolicum

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Regel continued to increase the ADG, but increased rate was lower in test group 3 At d

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60, ADG of the 3 test groups was much higher than that of the control group (P < 0.05);

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the ADG of test group 2 was the highest, but it did not differ significantly from the

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ADG of the other 2 test groups (P > 0.05)

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3.1.2 Average daily feed intake

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The analysis showed the experimental time and treatment had an interaction effect,

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and the F value was 12.34 Table 2 shows flavonoids from Allium mongolicum Regel

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could improve the daily feed intake (DFI) of sheep After 15 d of feeding, the DFI did

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not differ among groups, nor did the test groups exhibit any significant alteration (P >

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0.05) compared with the control group However, starting at d 30, the DFI of all groups

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gradually changed; the DFI of test group 3 was the highest and significantly higher

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than that of the control group (P < 0.05) After d 45, the DFI of the 3 test groups

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showed an increasing trend but no big difference (P > 0.05), and their DFI were higher

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than that of the control group At d 60, the DFI of all groups showed increases, but

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those of 3 test groups were significantly higher than that of the control group (P <

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0.05) At d 60, the DFI of test group 3 was the highest, but it did not differ significantly

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from that of other 2 test groups (P > 0.05) Thus, when the experimental time was 60 d,

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the basal diet supplemented with 33 mg/kg flavonoids groups plays an important role

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to the DFI

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3.1.3 Feed conversion ratio

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The results showed the experimental time and treatment had an interaction effect,

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and the F value was 3.1 Table 2 indicates after d 15, basal diet supplement with

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flavonoids from Allium mongolicum Regel had no obvious effect on the feed

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conversion ratio (P > 0.05) After d 30, the feed conversion ratios of the 3 test groups

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decreased and were significantly lower than that of the control group (P < 0.05) At 45

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d, the feed conversion ratios of all groups continued to decrease, with the same

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difference among groups, and the feed conversion ratio of test group 2 was the lowest

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(P < 0.05) From d 45 to 60, the feed conversion ratios of the 3 test groups were

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significantly lower than that of the control group (P < 0.05) The feed conversion ratio

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of test group 3 was lower than that of test group 2, by an insignificant amount (P >

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0.05), and was significantly lower than that of test group 1 (P < 0.05) The flavonoids

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from Allium mongolicum Regel affected the feed conversation ratio from d 30, and the

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effect of test group 3 was the best, until d 60, the feed conversion ratio in test group 3

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was the lowest

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3.2 Serum GH, IGF-1, ACTH and CORT contents in sheep

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3.2.1 Serum GH levels

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At d 45, the content of serum GH was significantly changed (P < 0.05), and

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increased until d 60 when the content was the highest But the results indicated the

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experimental time and treatment did not have interaction effect (F = 1.48) Thus, Table

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3 is the analysis of treatment; it shows at d 0, the GH levels of the control group and

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test groups showed no obvious change (P > 0.05) At d 15, the GH content of test

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group 1 was higher than that of the control group (P < 0.05), but no significant

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difference among test groups (P > 0.05) At d 30, the GH content of the control group

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increased but did not differ significantly from those of other groups (P > 0.05) After d

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45, the GH contents of all 3 test groups were higher than that of the control group (P <

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0.05), but values of test group 2 and 3 did not differ significantly (P > 0.05) After d 60,

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the GH contents of test groups 1 and 2 were higher than that of the control group (P <

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0.05), but there was no significant difference between groups in the amount of GH

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change (P > 0.05) The GH content showed an increasing trend with feeding time, and

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after d 45, the GH content showed significant changes (P < 0.05) Although there were

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no interaction effect on the experimental time and treatment, but at d 60, the test group

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2 exerted its’ best effect on the content of GH levels

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3.2.2 Serum IGF-1 content

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The content of serum IGF-1 was affected by experimental time Result shows

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from d 30 the serum content was changed (P < 0.05) And the results indicated the

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experimental time and treatment did not have interaction effect (F = 0.72) Table 3

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clearly shows at d 0, the addition of flavonoids from Allium mongolicum Regel to the

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basal diet had no obvious effect on the serum IGF-1 content, and the control group and

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all test groups did not show significant differences (P > 0.05) At d 15, the IGF-1

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content increased in all test groups with no significant difference (P > 0.05);

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furthermore, the increase since d 0 was not significant (P > 0.05) After d 30, the

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IGF-1 content of the 3 test groups increased with no significant changes compared with

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that of the control group (P > 0.05) Forty-five days later, the IGF-1 contents of test

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groups 1 and 3 became significantly higher than that of the control group (P < 0.05)

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and non-significantly higher than that of test group 2 (P > 0.05) The IGF-1 contents of

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3 groups were significantly higher than that of the control group at d 60 (P < 0.05); test

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group 3 had the highest IGF-1 levels at this time point, but with no significant

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difference (P > 0.05) The IGF-1 content was the highest after 60 d of feeding and

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showed significant changes (P < 0.05) compared with the contents at d 0 and 15 But

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there were no interaction effect between the experimental time and treatment, thus the

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basal diet supplemented with 33 mg/kg flavonoids from Allium mongolicum Regel and

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fed 60 d would play the best role in the secretion of serum IGF-1

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3.2.3 Serum CORT content

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Result shows at d 30 of feeding, the content of serum CORT level was changed

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obviously (P < 0.05), and at d 45 and 60, the content was higher than values at d 0, 15

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and 30 (P < 0.05) Table 3 shows the basal diet with flavonoids from Allium

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mongolicum Regel did not lead to variations in the serum CORT content (P > 0.05) at

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d 0 After 15 d of feeding, the CORT contents of all test groups decreased, and test

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groups 2 and 3 showed the lowest levels; however, there was no significant difference

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between any of the test groups and the control group (P > 0.05) At d 30, all test groups

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still showed a decreasing trend, and the CORT content of test group 2 was significantly

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lower than that of the control group (P <0.05) and non-significantly lower than those

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of the other 2 test groups (P > 0.05) At d 45, all of the CORT contents of the 3 test

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groups and the control group decreased; the CORT contents of the 3 test groups were

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lower than that of the control group with no significant difference (P > 0.05) At d 60,

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the CORT contents of the 3 test groups were lower than that of the control group, still

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not to a significant degree (P > 0.05) These findings indicate the flavonoids from

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Allium mongolicum Regel could decrease the serum CORT contents in sheep At d 60,

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the content of serum CORT in 3 test groups was the highest

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3.2.4 Serum ACTH content

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Results indicated feeding time affected the serum ACTH levels from d 30 (P <

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0.05), and the contents at d 45 and 60 were higher than the level at d 30 (P < 0.05)

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