Serum Metabolomics of <i>Ophiopogon japonicus</i> Extract Against Type 2 Diabetes in Mice

doi:10.13523/j.cb.2209009

China Biotechnology

2022, Vol. 42

Issue (11): 99-108 DOI: 10.13523/j.cb.2209009

Serum Metabolomics of Ophiopogon japonicus Extract Against Type 2 Diabetes in Mice

ZHANG Jie^1,², LIN Bing-feng², XU Ping-cui², WANG Na-ni², CHEN Yu^1,^**(

)

1 Hangzhou Vocational & Technical College, Hangzhou 310018, China
2 Zhejiang Academy of Traditional Chinese Medicine, Hangzhou 310007, China

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Abstract

Objective: To study the protective mechanism of Ophiopogon japonicus extract on Type 2 diabetes mellitus (T2DM) based on metabolomics. Methods: The T2DM mouse model was established by intraperitoneal injection of streptozotocin. Mice were orally administrated with the aqueous extract of Ophiopogon japonicu for 4 weeks. The diabetic phenotypes in serum were measured. Changes in serum metabolites were determined by ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS). Results: Compared with the control group, the fasting glucose, total cholesterol, triglyceride, and low-density lipoprotein cholesterol were increased in the model group, while the high-density lipoprotein cholesterol decreased significantly, and the above indexes were reversed after treatment of Ophiopogon japonicus extract. The metabonomic results showed that 43 differential metabolites were found between the control group and the model group. These metabolites were enriched in 18 pathways. Ophiopogon japonicus extract significantly decreased the content of glyceric acid, malonic semialdehyde, and 4-hydroxyphenylpyruvic acid in T2DM mice. Ophiopogon japonicus extract could regulate 7 pathways, such as ubiquinone and other terpenoid-quinone biosynthesis. Conclusion: The hypoglycemic and lipid-lowering effect of Ophiopogon on T2DM may be related to ubiquinone and other terpenoid-quinone biosynthesis.

Key words： Metabonomics Type 2 diabetes Ophiopogon japonicas Serum UPLC-Q/TOF-MS

Received: 03 September 2022 Published: 07 December 2022

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	ZHANG Jie
	LIN Bing-feng
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	WANG Na-ni
	CHEN Yu

Cite this article:

ZHANG Jie, LIN Bing-feng, XU Ping-cui, WANG Na-ni, CHEN Yu. Serum Metabolomics of Ophiopogon japonicus Extract Against Type 2 Diabetes in Mice. China Biotechnology, 2022, 42(11): 99-108.

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https://manu60.magtech.com.cn/biotech/10.13523/j.cb.2209009 OR https://manu60.magtech.com.cn/biotech/Y2022/V42/I11/99

Fig.1 Effect of Ophiopogon japonicus on the levels of FBG, TC, TG, LDL-C and HDL-C in serum of T2DM model mice

x -

±s,n=6,^* P<0.05; ^** P<0.01

Fig.2 PCA 3D score plots

Fig.3 PLS-DA score plots

Fig.4 OPLS-DA score plots and Permutation test charts

编号	HMDB号	代谢物		质荷比 (m/z)		保留时间 /min		分子式		加合物		正常组 vs.模型组		模型组 vs.麦冬组
1	HMDB0000700	Hydroxypropionic acid		71.013 8		0.06		C₃H₆O₃		M-H₂O-H		↓^**		↓
2	HMDB0011111	Malonic semialdehyde		87.008 7		9.58		C₃H₄O₃		M-H		↓^*		↑^*
3	HMDB0000139	Glyceric acid		87.008 7		8.01		C₃H₆O₄		M-H₂O-H		↓^*		↑^*
4	HMDB0000630	Cytosine		92.025 3		19.84		C₄H₅N₃O		M-H₂O-H		↑^**		↑
5	HMDB0000718	Isovaleric acid		101.060 7		12.14		C₅H₁₀O₂		M-H		↓^**		↑
6	HMDB0000019	Alpha-ketoisovaleric acid		115.040 0		0.06		C₅H₈O₃		M-H		↓^**		↑
7	HMDB0000227	Mevalonic acid		129.055 7		5.34		C₆H₁₂O₄		M-H₂O-H		↑^**		↓
8	HMDB0001644	D-Xylulose		131.034 9		3.09		C₅H₁₀O₅		M-H₂O-H		↓^**		↑
9	HMDB0006483	D-Aspartic acid		132.030 1		0.05		C₄H₇NO₄		M-H		↓^**		↓
10	HMDB0000157	Hypoxanthine		135.031 3		10.56		C₅H₄N₄O		M-H		↓^**		↑
11	HMDB0000635	Succinylacetone		139.040 0		9.60		C₇H₁₀O₄		M-H₂O-H		↓^**		↑
12	HMDB0000819	Normetanephrine		164.071 7		7.63		C₉H₁₃NO₃		M-H₂O-H		↓		↓^*
13	HMDB0014634	Miglitol		188.092 7		1.88		C₈H₁₇NO₅		M-H₂O-H		↓^**		↓
14	HMDB0000291	Vanillylmandelic acid		197.045 4		9.84		C₉H₁₀O₅		M-H		↓^*		↑
15	HMDB0006059	20-Carboxy-leukotriene B4		347.186 1		9.38		C₂₀H₂₈O₅		M-H20-H		↓^*		↓
16	HMDB0012136	1-Amino-propan-2-ol		76.076 3		0.92		C₃H₉NO		M+H		↑^*		↓
17	HMDB0000097	Choline		86.096 9		1.10		C₅H₁₄NO		M+H-H₂O		↓^**		↓
18	HMDB0033827	(2E)-2-Heptenal		95.085 9		0.60		C₇H₁₂O		M+H-H₂O		↑^**		↓
19	HMDB0002362	2,4-Diaminobutyric acid		101.071 2		14.00		C₄H₁₀N₂O₂		M+H-H₂O		↓^*		↑
20	HMDB0000459	3-Methylcrotonylglycine		140.070 4		10.70		C₇H₁₁NO₃		M+H-H₂O		↓^**		↓
21	HMDB0000182	L-Lysine		147.112 6		10.59		C₆H₁₄N₂O₂		M+H		↑^*		↑
22	HMDB0000205	Phenylpyruvic acid		165.054 3		0.11		C₉H₈O₃		M+H		↑^*		↑
23	HMDB0000159	L-Phenylalanine		166.086 1		2.91		C₉H₁₁NO₂		M+H		↓^**		↓
24	HMDB0001431	Pyridoxamine		169.096 9		1.09		C₈H₁₂N₂O₂		M+H		↓^**		↑
25	HMDB0000446	N-alpha-acetyl-L-lysine		171.112 5		1.08		C₈H₁₆N₂O₃		M+H-H₂O		↓^**		↓
26	HMDB0000701	Hexanoylglycine		174.112 3		8.11		C₈H₁₅NO₃		M+H		↓^**		↓
27	HMDB0014018	4-Hydroxypropofol		177.127 1		15.79		C₁₂H₁₈O₂		M+H-H₂O		↑^**		↑^*
28	HMDB0000707	4-Hydroxyphenylpyruvic acid		181.049 2		15.68		C₉H₈O₄		M+H		↓^**		↑^*
29	HMDB0000158	L-Tyrosine		182.080 8		7.09		C₉H₁₁NO₃		M+H		↓^**		↑
30	HMDB0001024	Phosphohydroxypyruvic acid		184.985 1		16.48		C₃H₅O₇P		M+H		↓^**		↑
31	HMDB0002302	Indole-3-propionic acid		190.085 9		9.60		C₁₁H₁₁NO₂		M+H		↑^**		↓
32	HMDB0012948	Formyl-5-hydroxykynurenamine		191.080 9		1.11		C₁₀H₁₂N₂O₃		M+H-H₂O		↓^**		↑
33	HMDB0000350	3-Hydroxysebacic acid		201.111 8		10.70		C₁₀H₁₈O₅		M+H-H₂O		↓^**		↑
34	HMDB0013286	N-Undecanoylglycine		213.982 5		19.80		C₁₃H₂₅NO₃		M+H-H₂O		↑^**		↑^*
35	HMDB0011175	Leucylproline		229.154 1		1.08		C₁₁H₂₀N₂O₃		M+H		↓^**		↓
36	HMDB0011170	Gamma-glutamylisoleucine		261.143 9		6.61		C₁₁H₂₀N₂O₅		M+H		↓^**		↓^*
37	HMDB0013133	Methylmalonylcarnitine		262.127 9		1.06		C₁₁H₁₉NO₆		M+H		↑^*		↓
38	HMDB0004701	9,10-Epoxyoctadecenoic acid	279.230 9		14.57		C₁₈H₃₂O₃		M+H-H₂O		↑^**		↓
39	HMDB0000252	Sphingosine	282.278 5		16.11		C₁₈H₃₇NO₂		M+H-H₂O		↓^*		↓
40	HMDB0001388	Alpha-linolenic acid	301.215 0		13.39		C₁₈H₃₀O₂		M+H		↓^*		↑
41	HMDB0001043	Arachidonic acid	305.246 6		14.28		C₂₀H₃₂O₂		M+H		↓^**		↓^*
42	HMDB0000222	Palmitoylcarnitine	400.341 6		17.35		C₂₃H₄₅NO₄		M+H		↑^**		↑
43	HMDB0011760	Cer(d18:0/16:0)	540.534 1		16.33		C₃₄H₆₉NO₃		M+H		↓^**		↑
44	HMDB0010392	LysoPC[20:2(11Z,14Z)/0:0]	548.369 9		14.45		C₂₈H₅₆NO₇P		M+H		↓^**		↓。*

Table 1 Potential biomarkers of Ophiopogon japonicus in treatment of T2DM

Fig.5 Differential metabolite pathway map between the blank group and the model group (a) and differential metabolite pathway map between the Ophiopogon group and the model group(b) (a)a: Phenylalanine, tyrosine and tryptophan biosynthesis; b:Ubiquinone and other terpenoid-quinone biosynthesis; c: Phenylalanine metabolism; d: Alpha-linolenic acid metabolism; e: Arachidonic acid metabolism; f: Tyrosine metabolism; g: Pentose and glucuronate interconversions; h: Terpenoid backbone biosynthesis; i: Beta-alanine metabolism; j: Glycerolipid metabolism; k: Glyoxylate and dicarboxylate metabolism; l: Vitamin B₆ metabolism; m: Glycine, serine and threonine metabolism; n: Glycerophospholipid metabolism; o: Sphingolipid metabolism; p: Purine metabolism; q: Valine, leucine and isoleucine degradation; r: Propionate metabolism. (b)a: Ubiquinone and other terpenoid-quinones biosynthesis; b: Beta-alanine metabolism; c: Glycerolipid metabolism; d: Tyrosine metabolism; e: Glyoxylate and dicarboxylate metabolism; f: Glycine, serine and threonine metabolism; g: Propionate metabolism


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