Frankincense myrrh attenuates hepatocellular carcinoma by regulating tumor blood vessel development through multiple epidermal growth factor receptor-mediated signaling pathways

Table 1 The RNA sequences used in this study

Name	Primer sequence	Primer length
HIF-1α	F→TCCAGCAGACCCAGTTACAGA; R→GCCACTGTATGCTGATGCCTT	182bp
TNF-α	F→AGCACAGAAAGCATGATCCG; R→CACCCCGAAGTTCAGTAGACA	162bp
VEGF	F→GAACCAGACCTCTCACCGGAA; R→ACCCAAAGTGCTCCTCGAAG	135bp
MMP-9	F→GCCCTGGAACTCACACGACA; R→GTAGCCCACGTCGTCCACC	139bp
GAPDH	F→GCGACTTCAACAGCAACTCCC; R→CACCCTGTTGCTGTAGCCGTA	122bp

Table 2 The effective candidate ingredients of frankincense and myrrh

Mol ID	Molecule name	OB (%)	DL	Medicine
MOL001215	Tirucallol	42.12	0.75	Frankincense
MOL001241	O-acetyl-α-boswellic acid	42.73	0.70	Frankincense
MOL001243	3alpha-Hydroxy-olean-12-en-24-oic-acid	39.32	0.75	Frankincense
MOL001255	Boswellic acid	39.55	0.75	Frankincense
MOL001263	3-oxo-tirucallic, acid	42.86	0.81	Frankincense
MOL001265	Acetyl-alpha-boswellic,acid	42.73	0.70	Frankincense
MOL001272	Incensole	45.59	0.22	Frankincense
MOL001295	Phyllocladene	33.40	0.27	Frankincense
MOL000098	Quercetin	46.43	0.28	Myrrh
MOL000358	Beta-sitosterol	36.91	0.75	Myrrh
MOL000449	Stigmasterol	43.83	0.76	Myrrh
MOL000490	Petunidin	30.05	0.31	Myrrh
MOL000979	2-methoxyfuranoguaia-9-ene-8-one	66.18	0.18	Myrrh
MOL000988	4,17(20)-(cis)-pregnadiene-3,16-dione	51.42	0.48	Myrrh
MOL000996	Guggulsterol IV	33.59	0.74	Myrrh
MOL001001	Quercetin-3-O-β-D-glucuronide	30.66	0.74	Myrrh
MOL001002	Ellagic acid	43.06	0.43	Myrrh
MOL001004	Pelargonidin	37.99	0.21	Myrrh
MOL001006	Poriferasta-7,22E-dien-3beta-ol	42.98	0.76	Myrrh
MOL001009	Guggulsterol-VI	54.72	0.43	Myrrh
MOL001013	Mansumbinoic acid	48.10	0.32	Myrrh
MOL001019	(7S,8R,9S,10R,13S,14S,17Z)-17-ethylidene-7-hydroxy-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15-decahydrocyclopenta(a)phenanthrene-3,16-dione	35.75	0.48	Myrrh
MOL001021	7β,15β- dihydroxypregn-4-ene-3,16-dione	43.11	0.51	Myrrh
MOL001022	11α-hydroxypregna-4,17(20)-trans-diene-3,16-dione	36.62	0.47	Myrrh
MOL001026	Myrrhrrhanol C	39.96	0.58	Myrrh
MOL001027	Myrrhrrhanone A	40.25	0.63	Myrrh
MOL001028	(8R)-3-oxo-8-hydroxy-polypoda-13E,17E,21-triene	44.83	0.59	Myrrh
MOL001029	Myrrhrrhanones B	34.39	0.67	Myrrh
MOL001031	Epimansumbinol	61.81	0.40	Myrrh
MOL001033	Diayangambin	63.84	0.81	Myrrh
MOL001040	(2R)-5,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one	42.36	0.21	Myrrh
MOL001045	(13E,17E,21E)-8-hydroxypolypodo-13,17,21-trien-3-one	44.34	0.58	Myrrh
MOL001046	(13E,17E,21E)-polypodo-13,17,21-triene-3,18-diol	39.96	0.58	Myrrh
MOL001049	16-hydroperoxymansumbin-13(17)-en-3β-ol	41.05	0.49	Myrrh
MOL001052	Mansumbin-13(17)-en-3,16-dione	41.78	0.45	Myrrh
MOL001061	(16S,20R)-dihydroxydammar-24-en-3-one	37.34	0.78	Myrrh
MOL001062	15α-hydroxymansumbinone	37.51	0.44	Myrrh
MOL001063	28-acetoxy-15α-hydroxymansumbinone	41.85	0.67	Myrrh
MOL001069	3β-acetoxy-16β,20(R)-dihydroxydammar-24-ene	38.72	0.81	Myrrh
MOL001088	1α-acetoxy-9,19-cyclolanost-24-en-3β-ol	44.40	0.78	Myrrh
MOL001092	{(3R,5R,8R,9R,10R,13R,14R,17S)-17-[(2S,5S)-5-(2-hydroxypropan-2-yl)-2-methyloxolan-2-yl]-4,4,8,10,14-pentamethyl-2,3,5,6,7,9,11,12,13,15,16,17-dodecahydro-1H-cyclopenta(a)phenanthren-3-yl} acetate	33.07	0.80	Myrrh
MOL001093	Cabraleone	36.21	0.82	Myrrh
MOL001095	Isofouquierone	40.95	0.78	Myrrh
MOL001126	[(5aS,8aR,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5,5a,6,9-tetrahydroisobenzofurano(6,5-f)(1,3)benzodioxol-8a-yl] acetate	44.08	0.90	Myrrh
MOL001131	Phellamurin_qt	56.60	0.39	Myrrh
MOL001138	(3R,20S)-3,20-dihydroxydammar-24-ene	37.49	0.75	Myrrh
MOL001145	(20S)-3β-acetoxy-12β,16β,25-tetrahydroxydammar-23-ene	34.89	0.82	Myrrh
MOL001146	(20S)-3β,12β,16β,25-pentahydroxydammar-23-ene	37.94	0.75	Myrrh
MOL001147	(20R)-3β-acetoxy-16β-dihydroxydammar-24-ene	40.36	0.82	Myrrh
MOL001148	3β-hydroxydammar-24-ene	40.27	0.82	Myrrh
MOL001156	3-methoxyfuranoguaia-9-en-8-one	35.15	0.18	Myrrh
MOL001164	[(5S,6R,8R,9Z)-8-methoxy-3,6,10-trimethyl-4-oxo-6,7,8,11-tetrahydro-5H-cyclodeca(b)furan-5-yl] acetate	34.76	0.25	Myrrh
MOL001175	Guggulsterone	42.45	0.44	Myrrh

Table 3 Virtual docking of biologically active ingredients from frankincense and myrrh for hepatocellular carcinoma targets

Mol ID	Molecule name	Scores/(kcal∙mol-1)
		AKT1	VEGFA	EGFR
MOL000098	Quercetin	-7.6	-5.7	-7.2
MOL000358	Beta-sitosterol	-8.1	-6.9	-9.2
MOL000449	Stigmasterol	-8.6	-6.8	-9.6
MOL001243	3alpha-Hydroxy-olean-12-en-24-oic-acid	-8.7	-7.1	-8.3
MOL001255	Boswellic acid	-8.8	-7.0	-9.3