. 2017 Dec 13;8:893. doi: 10.3389/fphar.2017.00893

Table 3.

Identified compounds significantly changing over incubation time.

Peak ^#	Compound name	RT (min)	Monoisotopic mass	Molecular formula	Δ (ppm)	Human fecal suspension		PBS	Literature/database
						WBE (2 mg/ml)	WBE (10 mg/ml)	WBE (10 mg(/ml)
1	saccharose^b	1.33	342.1166	C₁₂H₂₂O₁₁	4.14
2	malic acid^b	1.43	134.0203	C₄H₆O₅	−1.35				https://metlin.scripps.edu/^b
3	citric acid^a	1.66	192.0263	C₆H₈O₇	1.94
4	succinic acid^a	1.96	118.0252	C₄H₆O₄	−2.42
5	isopropyl maleate^b	2.65	158.0565	C₇H₁₀O₄	−2.00				http://www.hmdb.ca/^b
6	protocatechuic acid^a ⁺	4.93	154.0252	C₇H₆O₄	−2.32				Goodrich and Neilson, 2014 ⁺
7	(epi)gallocatechin^b ^#	5.17	306.0742	C₁₅H₁₄O₇	5.12				https://metlin.scripps.edu/^b; Jürgenliemk et al., 2007 ^#
8	catechol^b	5.62	110.0352	C₆H₆O₂	−2.99				https://metlin.scripps.edu/^b
9	vanillic acid hexoside^b ^#	6.08	330.0957	C₁₄H₁₈O₉	5.26				Liao et al., 2014; Ammar et al., 2015 ^b
10	salicin^a ^#	6.72	286.1055	C₁₃H₁₈O₇	3.78				Agnolet et al., 2012 ^#; Kammerer et al., 2005 ^#
11	cysteine-saligenin-adduct^b	6.98	227.0611	C₁₀H₁₃O₃NS	1.94
12	saligenin^a ^#	7.06	124.0512	C₇H₈O₂	−1.51				Kammerer et al., 2005 ^#
13	5-(3',4',5'-trihydroxyphenyl)-γ-valerolactone^b ⁺	7.68	224.0677	C₁₁H₁₂O₅	1.26				Takagaki and Nanjo, 2010 ⁺
14	gentisic acid^a	7.70	154.0252	C₇H₆O₄	−2.25
15	4-hydroxybenzoic acid^a	7.72	138.0301	C₇H₆O₃	−3.51
16	4-hydroxy-5-(dihydroxyphenyl)valeric acid^b ⁺	8.88	226.0834	C₁₁H₁₄O₅	1.60				Takagaki and Nanjo, 2013 ^b ⁺
17	dihydrocaffeic acid^a ⁺	9.13	182.0570	C₉H₁₀O₄	2.01				Monagas et al., 2010 ⁺; Takagaki and Nanjo, 2013 ⁺
18	(epi)catechin-(epi)catechin^b ^#	9.23	578.1430	C₃₀H₂₆O₁₂	2.82				https://metlin.scripps.edu/^b, Jürgenliemk et al., 2007 ^#
19	catechin^a ^#	9.62	290.0793	C₁₅H₁₄O₆	4.59				Jürgenliemk et al., 2007 ^#
20	4-oxo-5-(dihydroxyphenylvaleric)acid^b ⁺	9.79	224.0677	C₁₁H₁₂O₅	1.26				Takagaki and Nanjo, 2013 ^b ⁺
21	dihydroxybenzoic acid^b	9.87	154.0251	C₇H₆O₄	−2.37				https://metlin.scripps.edu/^b
22	hydroxy(iso)caproic acid^b ⁺	10.52	132.0771	C₆H₁₂O₃	−3.74				http://www.hmdb.ca ^b; Zheng et al., 2011 ⁺
23	acetylsalicin^b ^#	10.54	328.1161	C₁₅H₂₀O₈	3.82				Yang et al., 2013 ^#; Kammerer et al., 2005 ^b ^#
24	hydroxy(iso)caproic acid⁺	10.88	132.0771	C₆H₁₂O₃	−3.68				http://www.hmdb.ca ^b; Zheng et al., 2011 ⁺
25	chlorogenic acid^a ^#	10.92	354.0955	C₁₆H₁₈O₉	4.48				Zaiter et al., 2016 ^#
26	(epi)catechin-(epi)catechin-(epi)catechin^b ^#	10.95	866.2067	C₄₅H₃₈O₁₈	2.47				Jürgenliemk et al., 2007; Bijttebier et al., 2016 ^b; Piccinelli et al., 2016; Zaiter et al., 2016 ^#
27	syringin^b ^#	11.38	372.1421	C₁₇H₂₄O₉	4.44				Agnolet et al., 2012 ^#; Tótha et al., 2016 ^b
28	5-(dihydroxyphenyl)-y-valerolactone^b ⁺	12.34	208.0726	C₁₁H₁₂O₄	0.07				Goodrich and Neilson, 2014 ^b ⁺; Takagaki and Nanjo, 2013
29	benzyl-hexoside-pentoside^b	12.40	402.1539	C₁₈H₂₆O₁₀	4.50				Delgado De La Torre et al., 2015 ^b
30	ampelopsin^b ^#	12.42	320.0533	C₁₅H₁₂O₈	4.16				Agnolet et al., 2012 ^#; Yang et al., 2012 ^b
31	diyhdroquercetin sulfate^b	12.83	314.0156	C₁₅H₁₂O₁₀S	1.56				Vacek et al., 2013 ^b
32	benzyl-hexoside-pentoside^b	12.89	402.1541	C₁₈H₂₆O₁₀	4.95				Delgado De La Torre et al., 2015 ^b
33	acetylsalicin^b ^#	14.39	328.1159	C₁₅H₂₀O₈	3.42				Kammerer et al., 2005 ^b ^#
34	3-(3-hydroxyphenyl)propionic acid^a ⁺	14.65	166.0616	C₉H₁₀O₃	−1.88				Takagaki and Nanjo, 2013 ⁺
35	4-hydroxy-5-(hydroxyphenyl))valeric acid^b ⁺	16.61	210.0882	C₁₁H₁₄O₄	0.55				Takagaki and Nanjo, 2013 ^b ⁺
36	dihydroquercetin^a ^#	17.78	304.0585	C₁₅H₁₂O₄	4.62				Agnolet et al., 2012 ^#
37	(+)-naringenin-5-glucoside^b ^#	17.89	434.1215	C₂₁H₂₂O₁₀	3.64				Kammerer et al., 2005 ^#
38	salicylic acid^a ^#	17.99	138.0302	C₇H₆O₃	−3.29				Kammerer et al., 2005 ^#
39	rosarin^b	18.34	428.1683	C₂₀H₂₈O₁₀	3.08				Tolonen et al., 2003 ^b
40	salicortin^b ^#	18.49	424.1371	C₂₀H₂₄O₁₀	1.79				Kammerer et al., 2005 ^b ^#
41	(-)-naringenin-5-glucoside^b ^#	18.84	434.1215	C₂₁H₂₂O₁₀	3.09				Kammerer et al., 2005 ^b ^#
42	5-(dihydroxyphenyl)valeric acid^b ⁺	19.65	210.0882	C₁₁H₁₄O₄	0.31				Takagaki and Nanjo, 2013 ^b ⁺
43	cinnamyl-(6‘-O- xylopyranosyl)-O-glucopyranoside^b	19.66	428.1690	C₂₀H₂₈O₁₀	2.94				Tolonen et al., 2003 ^b
44	hyperoside^a ^#	20.70	464.0957	C₂₁H₂₀O₁₂	4.27				Nybakken and Julkunen-Tiitto, 2013 ^#
45	cinnamyl-hexoside-deoxyhexoside^b	20.95	442.1840	C₂₁H₃₀O₁₀	2.80				https://metlin.scripps.edu/^b
46	dihydrocinnamylhexoside-deoxyhexoside^b	21.52	444.2001	C₂₁H₃₂O₁₀	3.42				Tolonen et al., 2004 ^b
47	naringenin-7-glucoside^a ^#	21.90	434.1215	C₂₁H₂₂O₁₀	1.58				Kammerer et al., 2005 ^#
48	salireposide^b ^#	22.34	406.1268	C₂₀H₂₂O₉	3.28				Kammerer et al., 2005 ^b ^#
49	phenylpropionic acid^b ⁺	24.15	150.067	C₉H₁₀O₂	−0.35				http://www.hmdb.ca ^b; Rechner et al., 2004; Goodrich and Neilson, 2014; Orrego-Lagarón et al., 2016 ⁺
50	acetylsalicortin^b ^#	24.79	466.1475	C₂₂H₂₆O₁₁	1.86				Kammerer et al., 2005 ^b ^#
51	grandidentatin/isograndidentatin^b ^#	24.97	424.173	C₂₁H₂₈O₉	4.23				Yang et al., 2013 ^#; Jervis et al., 2015 ^b
52	isosalipurposide^b ^#	25.40	434.1211	C₂₁H₂₂O₁₀	3.99				Kammerer et al., 2005 ^b ^#
53	grandidentatin/isograndidentatin^b ^#	25.46	424.174	C₂₁H₂₈O₉	4.02				Yang et al., 2013 ^#; Jervis et al., 2015 ^b
54	hydroxyphenylvaleric acid^b ⁺	25.87	194.093	C₁₁H₁₄O₃	0.00				Takagaki and Nanjo, 2013 ^b ⁺
55	benzoylsalicin^b ^#	27.51	390.132	C₂₀H₂₄O₉	3.07				Kammerer et al., 2005 ^b ^#
56	naringenin^a ^#	30.77	272.0683	C₁₅H₁₂O₅	4.58				Freischmidt et al., 2012 ^#
57	HCH-acetylsalicortin^b ^#	32.46	604.1893	C₂₉H₃₂O₁₄	2.45				Merken and Clausen, 1992 ^#; Keefover-Ring et al., 2014 ^b
58	tremulacin^b ^#	35.54	528.163	C₂₇H₂₈O₁₁	1.73				Kammerer et al., 2005 ^b ^#

Compounds 1–58 were undetectable in the vehicle control samples. Therefore, they can be assumed to be derived from willow bark extract or its metabolites.

Identified by comparison with authentic reference compound.

Tentative identification based on monoisotopic mass and comparison with fragmentation patterns in literature or databases (HMDB, Metlin, Massbank, mzCloud; for details, see Supplementary Data Sheet 1); structural isomers cannot be ruled out;

Described in the literature in Salix sp;

⁺

Described in the literature as intestinal/fecal metabolite.

Color code:

Inline graphic Decreasing over 24 h (ratio t0/t24 < 0.5, p < 0.05).

Inline graphic Newly formed or increasing over 24 h (ratio t0/t24 >2, p < 0.05).

Inline graphic Intermediate (ratio t0/t4 > 2, p < 0.05; ratio t4/t24 > 1.25).

Inline graphic No significant change over 24 h.

Inline graphic Not detectable.