Integrated metabolomic profiling for analysis of antilipidemic effects of Polygonatum kingianum extract on dyslipidemia in rats

doi:10.3748/wjg.v24.i48.5505

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Basic Study

World J Gastroenterol. Dec 28, 2018; 24(48): 5505-5524
Published online Dec 28, 2018. doi: 10.3748/wjg.v24.i48.5505

Table 1 Body weight and food intake of rats

	Normal control	Model	Simvastatin	*P. kingianum*
Initial body weight (g)	200.87 ± 8.83	206.69 ± 8.51	205.03 ± 6.26	206.72 ± 7.82
Final body weight (g)	494.81 ± 37.43	518.08 ± 40.50	487.62 ± 30.26	480.14 ± 29.91
Body weight gain (g)	293.94 ± 28.61	311.39 ± 31.98	282.59 ± 24.01	273.42 ± 22.10
Food intake (g)	15670.81	15042.53	14969.08	14903.86

Values represent the mean ± SD from five animals. P. kingianum: Polygonatum kingianum.

Table 2 Effects of Polygonatum kingianum on total cholesterol and triglyceride concentrations in rat serum

Group	TC (mmol/L)	TG (mmol/L)
Normal group	1.42 ± 0.11^c	0.91 ± 0.21
Model group	1.56 ± 0.11^a	0.97 ± 0.22
P. kingianum group	1.43 ± 0.13^c	0.76 ± 0.13^c
Simvastatin group	1.15 ± 0.09^b^d	0.77 ± 0.09^c

Values represent the mean ± SD from five animals.

^aP < 0.05,

^bP < 0.01 vs the relative normal group.

^cP < 0.05,

^dP < 0.01 vs the relative model group. P. kingianum: Polygonatum kingianum; TC: Total cholesterol; TG: Triglyceride.

Table 3 Effects of Polygonatum kingianum on total cholesterol and triglyceride concentration in rat liver

Group	TC (mmol/gprot)	TG (mmol/gprot)
Normal group	0.77 ± 0.19^d	1.46 ± 0.12^d
Model group	1.17 ± 0.22^b	2.83 ± 0.71^b
P. kingianum group	0.95 ± 0.15^c	1.20 ± 0.28^d
Simvastatin group	0.94 ± 0.15^c	1.37 ± 0.43^d

Values represent the mean ± SD from five animals. ^aP < 0.05,

^bP < 0.01 vs the relative normal group.

^cP < 0.05,

^dP < 0.01 vs the relative model group. P. kingianum: Polygonatum kingianum; TC: Total cholesterol; TG: Triglyceride.

Table 4 Potential biomarkers identified from serum samples

Retention time (min)	Molecular weight (Da)	VIP	Potential biomarker	Formula	Change trend
Retention time (min)	Molecular weight (Da)	VIP	Potential biomarker	Formula	Model-PKRP
ESI-
0.928261	215.032	6.26699	2-C-Methyl-D-erythritol 4-phosphate	C₅H₁₃O₇P	down
8.30572	245.048	2.59774	Pimpinellin	C₁₃H₁₀O₅	down
17.7034	327.233	1.53493	3-Methyl-5-pentyl-2-furannonanoic acid	C₁₉H₃₂O₃	down
13.0574	437.291	1.03338	4,4'-Diaponeurosporene	C₃₀H₄₂	up
ESI+
1.11629	132.102	21.806	Isoleucine	C₆H₁₃NO₂	down
0.997628	132.077	16.0576	3-Guanidinopropanoate	C₄H₉N₃O₂	up
1.0913	118.087	14.9589	Aminopentanoic acid	C5H₁₁NO₂	up
15.9773	496.338	14.2141	LysoPC(16:0)	C₂₄H₅₀NO₇P	up
2.1554	166.086	11.8849	L-Phenylalanine	C₉H₁₁NO₂	down
5.46147	205.097	10.6298	L-Tryptophan	C₁₁H₁₂N₂O₂	up
0.9767	203.053	10.4336	α-D-Glucose	C₆H₁₂O₆	down
18.5687	400.332	9.59788	Palmitoyl-L-carnitine	C₂₃H₄₅NO₄	down
1.09687	150.058	9.09347	L-Methionine	C₅H₁₁NO₂S	down
1.10844	182.081	8.07313	L-Tyrosine	C₉H₁₁NO₃	up
5.6576	202.086	6.72953	2'-Aminobiphenyl-2,3-diol	C₁₂H₁₁NO₂	down
6.83329	160.096	6.65796	4-Hydroxystachydrine	C₇H₁₃NO₃	up
0.960596	140.068	6.04106	Pentanoic acid	C₅H₁₁NO₂	down
15.0993	478.306	1.00334	1-Oleoyl lysophosphatidic acid	C₂₁H₄₁O₇P	down
10.4394	288.216	2.12052	L-Octanoylcarnitine	C₁₅H₂₉NO₄	down

VIP: Variable importance in the projection.

Table 5 Potential biomarkers identified from urine samples

Retention time (min)	Molecular weight (Da)	VIP	Potential biomarker	Formula	Change trend
Retention time (min)	Molecular weight (Da)	VIP	Potential biomarker	Formula	Model-PKRP
ESI-
9.00895	213.113	1.42124	2,2'-(3-Methylcyclohexane-1,1-diyl) diacetic acid	C₁₁H₁₈O₄	up
3.93717	218.103	1.32234	Pantothenic acid	C₉H₁₇NO₅	up
14.0675	265.148	1.35019	Cumanin	C₁₅H₂₂O₄	up
1.11379	254.981	1.3057	Ascorbate-2-sulfate	C₆H₈O₉S	down
0.990052	308.099	1.2533	N-Acetylneuraminic acid	C₁₁H₁₉NO₉	down
3.03597	365.135	1.15211	Tetrahydropentoxyline	C₁₇H₂₂N₂O₇	down
17.8994	303.233	1.12374	Arachidonic acid	C₂₀H₃₂O₂	up
ESI+
8.40988	173.117	1.51559	4-Hydroxynonenoic acid	C₉H₁₆O₃	up
6.14752	172.007	1.50165	L-Homocysteine sulfonic acid	C₃H₉NO₃S₂	up
10.4959	187.126	1.47714	1-Phenyl-5-propyl-1H-pyrazole	C₁₂H₁₄N₂	up
8.40656	155.106	1.46075	4-Oxo-2-nonenal	C₉H₁₄O₂	up
8.2458	190.115	1.44948	N6-Carbamoyl-DL-lysine	C₇H₁₅N₃O₃	up
1.89902	213.123	1.39163	Butethal	C₁₇H₂₂N₂O₇	up
13.7859	256.263	1.38483	Palmitic amide	C₁₆H₃₃NO	up
6.67969	172.097	1.34087	(3-Methylcrotonyl)glycine methyl ester	C₈H₁₃NO₃	up
17.9836	315.252	1.33499	9,10-DiHOME	C₁₈H₃₄O₄	up
3.91979	220.118	1.30061	Pantothenic acid	C₉H₁₇NO₅	up
7.08734	192.066	1.26102	5-Hydroxyindoleacetic acid	C₁₀H₉NO₃	up
0.839605	146.165	1.24838	Spermidine	C₇H₁₉N₃	up
0.924092	170.093	1.24502	1-Methylhistidine	C₇H₁₁N₃O₂	up
1.09509	189.123	1.23644	N-Alpha-acetyllysine	C₈H₁₆N₂O₃	up
9.40433	139.112	1.20585	2-Pentylfuran	C₉H₁₄O	up
7.33104	143.107	1.20454	2-Octenoic acid	C₈H₁₄O₂	up
3.91714	222.122	1.19506	Vinyl-L-NIO	C₉H₁₇N₃O₂	up

VIP: Variable importance in the projection.

Table 6 Potential biomarkers identified from liver samples

Retention time (min)	Molecular weight(Da)	VIP	Potential biomarker	Formula	Change trend
Retention time (min)	Molecular weight(Da)	VIP	Potential biomarker	Formula	Model-PKRP
ESI-
3.95787	218.103	9.02621	Pantothenic acid	C₉H₁₇NO₅	up
5.52016	203.082	5.17533	L-Tryptophan	C₁₁H₁₂N₂O₂	up
17.9144	303.232	2.67441	Arachidonic acid	C₂₀H₃₂O₂	up
8.18557	241.073	2.08795	Lumichrome	C₁₂H₁₀N₄O₂	down
17.6944	327.233	2.03102	Docosahexaenoic acid	C₂₂H₃₂O₂	down
9.27129	201.112	1.77891	Sebacic acid	C10H18O₄	down
18.1942	279.232	1.75755	Linoleic acid	C₁₈H₃₂O2	up
11.3188	464.302	1.75082	Glycocholic acid	C₂₆H₄₃NO₆	down
13.9455	313.24	1.66517	9,10-DiHOME	C₁₈H₃₄O₄	down
15.9588	319.227	1.58662	16R-HETE	C₂₀H₃₂O₃	up
7.08734	353.234	1.56066	PGE1	C₂₀H₃₄O₅	up
10.8984	227.128	1.45155	Traumatic acid	C₁₂H₂₀O₄	down
2.5168	251.079	1.41613	Deoxyinosine	C₁₀H₁₂N₄O₄	down
11.4285	221.081	1.39399	Apiole	C₁₂H₁₄O₄	down
16.2815	339.199	1.28069	Canrenone	C₂₂H₂₈O₃	down
11.4127	351.219	1.14883	PGE2	C₂₀H₃₂O₅	up
15.6357	343.228	1.0584	Medroxyprogesterone	C₂₂H₃₂O₃	down
19.0468	281.249	1.03242	Ethyl palmitoleate	C₁₈H₃₄O₂	down
ESI+
5.58168	205.097	25.6421	L-Tryptophan	C₁₁H₁₂N₂O₂	up
1.12985	123.055	23.4569	Niacinamide	C₆H₆N₂O	up
3.94534	220.118	15.5283	Pantothenic acid	C₉H₁₇NO₅	down
1.07398	244.092	13.5445	Cytarabine	C₉H₁₃N₃O₅	down
1.65458	182.081	12.3842	L-Tyrosine	C₉H₁₁NO₃	up
0.901697	132.077	8.82297	3-Guanidinopropanoate	C₄H₉N₃O₂	down
0.990524	203.053	8.06945	L-(+)-Gulose	C₆H₁₂O₆	down
2.07851	269.088	7.66822	Inosine	C₁₀H₁₂N₄O₅	down
15.0942	302.305	7.59274	Sphinganine	C₁₈H₃₉NO₂	down
1.48196	153.04	7.19394	Xanthine	C₅H₄N₄O₂	down
6.38205	130.159	6.90221	Octylamine	C₈H₁₉N	down
1.21181	150.058	6.25979	L-Methionine	C₅H₁₁NO₂S	down
0.83538	146.165	6.24439	Spermidine	C₇H₁₉N₃	down
2.90983	285.083	5.64503	Xanthosine	C₁₀H₁₂N₄O₆	down
1.64612	165.055	5.16323	m-Coumaric acid	C₉H₈O₃	down
11.3366	181.122	4.58665	Dihydroactinidiolide	C₁₁H₁₆O₂	down
1.14382	204.123	4.29542	Succinylmonocholine	C₉H₁₇NO₄	down
2.20661	218.139	4.21655	Propionyl-L-carnitine	C₁₀H₁₉NO₄	down
5.73361	114.092	3.42289	ε-Caprolactam	C₆H₁₁NO	down
17.9613	305.248	1.8771	Arachidonic acid	C₂₀H₃₂O₂	up
13.2435	299.201	1.60893	Norethindrone	C₂₀H₂₆O₂	down
11.7171	181.122	1.58994	Dihydroactinidiolide	C₁₁H₁₆O₂	down

VIP: Variable importance in the projection.

Table 7 Results of metabolic pathway analysis of serum samples

No.	Pathway	Match status	P value	Impact	Details
1	Phenylalanine, tyrosine and tryptophan biosynthesis	2/4	8.19E-04	1.0	KEGG
2	Phenylalanine metabolism	2/9	0.0047415	0.40741	KEGG
3	Valine, leucine and isoleucine biosynthesis	1/11	0.126	0.33333	KEGG
4	Starch and sucrose metabolism	1/23	0.24635	0.18783	KEGG
5	Glycerophospholipid metabolism	1/30	0.30916	0.19753	KEGG
6	Tryptophan metabolism	1/41	0.39801	0.15684	KEGG
7	Tyrosine metabolism	1/42	0.40552	0.14045	KEGG

KEGG: Kyoto Encyclopedia of Genes and Genomes.

Table 8 Results of metabolic pathway analysis in urine samples

No.	Pathway	Match status	P value	Impact	Details
1	Arachidonic acid metabolism	1/36	0.20927	0.32601	KEGG

KEGG: Kyoto Encyclopedia of Genes and Genomes.

Table 9 Results of metabolic pathway analysis in liver samples

No.	Pathway	Match status	P value	Impact	Details
1	Arachidonic acid metabolism	3/36	0.042685	0.34677	KEGG
2	Phenylalanine, tyrosine and tryptophan biosynthesis	1/4	0.085643	0.5	KEGG
3	Linoleic acid metabolism	1/5	0.10592	1.0	KEGG
4	Nicotinate and nicotinamide metabolism	1/13	0.25318	0.2381	KEGG
5	Sphingolipid metabolism	1/21	0.37685	0.14286	KEGG
6	Tryptophan metabolism	1/41	0.60553	0.15684	KEGG
7	Tyrosine metabolism	1/42	0.61452	0.14045	KEGG

KEGG: Kyoto Encyclopedia of Genes and Genomes.

Citation: Yang XX, Wei JD, Mu JK, Liu X, Dong JC, Zeng LX, Gu W, Li JP, Yu J. Integrated metabolomic profiling for analysis of antilipidemic effects of Polygonatum kingianum extract on dyslipidemia in rats. World J Gastroenterol 2018; 24(48): 5505-5524
URL: https://www.wjgnet.com/1007-9327/full/v24/i48/5505.htm
DOI: https://dx.doi.org/10.3748/wjg.v24.i48.5505