The genus Scrophularia: a source of iridoids and terpenoids with a diverse biological activity

Figures & data

Figure 1. Comparison between chemical compounds isolated from investigated Scrophularia species. Part (A) shows investigated species percentage against the total species. Part (B) shows the relative percent of the various phytochemical class isolated from investigated Scrophularia species.

Table 1. The traditional use of Scrophularia species mentioned in different pharmacopoeias.

Name	Plant medicinal part	Traditional uses	Pharmacopeia	Other references
S. ningopoensis “Xuan Shen” (Chinese figwort)	Roots	Anti-inflammatory, treatment of cancer and antioxidant	Pharmacopoeia of the People’s Republic of China (Commission 2005) Society of Japanese Pharmacopoeia (Pharmacopoeia 2006)	Marty (1999), Wang et al. (2005) and Zhu (1998)
S. aquatica (water figwort) S. marilandica (late figwort)	Roots and aerial parts	Laxative, heart stimulant, circulatory stimulant and diuretic	The Pharmacopoeia of the Royal College of the Physicians at Edinburgh, Materia Medica (Lewis et al. 1748) French Pharmacopoeia (Ministry of Health 2012)	Marty (1999)
S. buergeriana “Bei xuan shen”	Roots	Treatment of fever, swelling, constipation, pharyngitis, neuritis and laryngitis	Pharmacopoeia of the People’s Republic of China (Commission 2005)	Pinkas et al. (1994) and Wang et al. (2005)
S. dentata “Ye-Xin-Ba” (Tabatian figwort)	Aerial parts	Treatment of smallpox, measles, high-heat plague and poisoning	Pharmacopoeia of the People’s Republic of China (Commission 2005)	Zhang et al. (2014)
S. nodosa (common figwort)	Roots and aerial parts	Treatment of Fever, swelling, constipation, pharyngitis, neuritis and laryngitis	French Pharmacopoeia (Ministry of Health, 2012) British Herbal Pharmacopoeia (Willoughby et al. 1996)	Zhu (1998)
S. lucida L. ”Sinderitis”	Roots and aerial parts	Heart stimulant, circulatory stimulant, diuretic	–	Goodyer and Gunther (1968)
S. chryasanthemifolia L. (Hetera sinderitis)	Roots and aerial parts	Heart stimulant, circulatory stimulant and diuretic	–	Goodyer and Gunther (1968)
S. canina “a ruta salvacce” (Ruta canina)	Roots	Treatment of dermatitis and rheumatoid arthritis	–	Berdini et al. (1991), Guarrera and Lucia (2007) and Pieroni et al. (2004)

Table 2. Compounds isolated from the genus Scrophularia (the structure of the compounds illustrated in text).

Plant name	Compound	No.	Ref.
S. auriculata	Scrovalentinoside	130	(Giner, et al. 2000, Giner et al. 1998)
	Verbascosaponin A	188
	Scropolioside A	134
	Ilwensisaponin A	177
	Verbascoside	48
S.amplexicaulis	Scropolioside D	131	(Pasdaran, et al. 2016)
	Scrophuloside B4	117
	Salidroside	75
	Verbascoside	48
	Eugenol	200
	Eugenol acetate	203
	1-Octen-3-ol	204
S. buergeriana	Buergerinin F	78	(Kim and Kim 2000, Lin, et al. 2000, Kim, et al. 2002b, Kim, et al. 2003b, Jeong et al. 2008, Yan and Xie 2011)
	Buergerinin G	79
	Buergerinin E	80
	Ningpogenin	86
	Buergerinin D	82
	Buergerinin C	84
	Buergerinin B	85
	8-O-E-p-methoxycinnamoyl harpagide	102
	8-O-Z-p-methoxycinnamoyl harpagide	103
	6′-O-E-p-methoxycinnamoyl harpagide	104
	6′-O-Z-p-methoxycinnamoyl harpagide	105
	Trans-cinnamic acid	11
	(E)-p-methoxycinnamic acid	12
	(E)-p-methoxycinnamic acid methyl ester	40
	(E)-o-methoxycinnamic acid	10
	(E)-p-coumaric acid	16
	(E)-caffeic acid	41
	(E)-ferulic acid	42
	Homovanilline alcohol	36
	Buergeriside A1	67
	Buergeriside B1	66
	Buergeriside B2	65
	Buergeriside C1	64
	Harpagoside	113
S. canina	7,8-Didehydro-6b,10-dihydroxy-11-noriridomyrmecin	83	(Berdini, et al. 1991, Venditti et al. 2015)
	8-epi-Loganic acid	138
	Verbascoside	48
	(E)-Phytol	174
S. cryptophila	Crypthophilic acid A	171	(Tasdemir, et al. 2008)
	Crypthophilic acid B	172
	Crypthophilic acid C	173
	Buddlejasaponin III	182
	8-O-Acetyl harpagide	100
	Harpagide	114
S. dentata	Scrodentoside A	139	(Zhang, et al. 2015b, Zhang, et al. 2014)
	Scrodentoside B	140
	Scrodentoside C	141
	Scrodentoside D	142
	Scrodentoside E	143
	Scrodentoside F	154
	Scrodentoside G	155
	Scrodentoside H	156
	Scropolioside G	157
	Scropolioside H	158
	Saccatoside	159
	6-O-Methyl catalpol	94
	Catalpol	93
	6′-O-E-p-feruloyl harpagide	107
	Scropolioside D	131
	Cis-harpagoside	144
	Harpagoside	113
	Laterioside	101
	Scorodioside	145
	6-O-α-L-(4″-O-trans-cinnamoyl)-rhamnopyranosylcatalpol	146
	6-O-α-L-(4″-O-trans-p-coumaroyl)-rhamnopyranosylcatalpol (Scropolioside F)	147
	lagotisoside D	148
	8-O-Acetyl harpagide	100
	7-Deoxygardoside	149
	Ajugoside	89
	8-epi-deoxyloganic acid	150
	6′-O-p-Coumaroyl harpagide	151
S. dentata (continued)	10-Deoxygeniposidic acid	152
	Geniposidic acid	153
	Ajugol	90
	Harpagide	114
	Scrodentoid A	195
	Scrodentoid B	196
	Scrodentoid C	197
	Scrodentoid D	198
	Scrodentoid E	199
	Lipedosides A-I	51
	Osmanthuside B	52
	Martynoside	53
	Diacetylmartynoside	54
	Verbascoside	48
	Isoverbascoside	49
	3-O-trans-Feruloylrhamnopyranose	76
	2-O-trans-Feruloylrhamnopyranose	77
S. deserti	3-(R)-1-Octan-3-yl-3-O-β-D-glucopyranoside	169	(Ahmed, et al. 2003, Stavri, et al. 2006)
	3(ζ)-Hydroxy-octadeca-4(E), 6(Z)-dienoic acid	170
	6-O-α-L-rhamnopyranosylcatalpol	97
	Buddlejoside A8	98
	Harpagoside B	99
	8-O-Acetyl harpagide	100
	Koelzioside	132
	Scropolioside D	131
	Scropolioside D2	133
	Scropolioside B	135
	Scrospioside A	136
	Laterioside	101
S. frutescens	(Z)-p-Coumaric acid	13	(Fernandez, et al. 1998, Garcia, et al. 1998)
	(Z)-Caffeic acid	14
	(Z)-Isoferulic acid	15
	(Z)-p-Methoxycinnamic acid	16
	(E)-p-coumaric acid	17
	(E) 3, 4-Dimethoxy cinnamic acid	18
	(Z) Ferulic acid	19
	(Z)-Methoxycinnamic acid methyl ester	20
	Syringic acid	21
	Gentisic acid	22
	Protocatechuic acid	23
	Isovanillic acid	24
	Catalpinic acid	25
	Vanillic acid	26
S. ilwensis	Ilwensisaponin A (Mimengoside A)	177	(Çalis, et al. 1993a, Çalis, et al. 1993b)
	Ilwensisaponin B	178
	Ilwensisaponin C	179
	Ilwensisaponin D	180
	Karsoside	116
	Scropolioside D	131
	Aucubin	109
	Harpagide	114
	8-O-Acetylharpagide	100
	Ajugol	90
	Angoroside C	46
	Quercetin-3-O-rutinoside	7
	Kaempferol-3-O-rutinoside	8
S. kakudensis	Songarosaponin A	189	(Yamamoto A 1993)
	Saksisaponin A	181
	Buddlejasaponin I	182
	Buddlejasaponin II	183
	Buddlejasaponin III	184
	Scrophulasaponin II	185
	Scrophulasaponin III	186
	Scrophulasaponin IV	187
S. koelzii	Koelzioside	132	(Bhandri et al. 1992, Garg, et al. 1994, Bhandari, et al. 1996, Bhandari, et al. 1997)
	Scropolioside A	134
	Scropolioside B	135
	6-O-(3”-O-p-Methoxy-cinnamoyl)-α-L-rhmanopyranosylcatalpol	161
	Scrokoelziside A	175
	Scrokoelziside B	176
S. lepidota	Ajugoside	89	(Tasdemir, et al. 2005)
	Ajugol	90
	Sinuatol	91
	6-O-β-D-Xylopyranosylaucubin	92
S. lepidota (continued)	Catalpol	93
	6-O-Methyl catalpol	94
	3,4-Dihydro-methyl catalpol	95
	1-Dehydroxy-3,4-dihydro aucubigenin	96
	Scrolepidoside	137
	Aucubin	109
	Angoroside C	46
	Ningpogenin	86
S. ningpoensis	Haemoplantaginin	4
	8-Hydroxycoumarin	38
	6-Hydroxyindan-1-one	39
	4-Methylcatechol	35
	trans-Cinnamic acid	10
	3-Methylphenyl-O-β-xylopyranosyl-(1→6)-O-β-glucopyranoside	70	(Kajimoto, et al. 1989, Qian, et al. 1991, Qian et al. 1992, Li, et al. 2000, Nguyen, et al. 2005, Chen, et al. 2007, Chen et al. 2008, Li, et al. 2009, Niu, et al. 2009, Zhang et al. 2012, Zhu et al. 2013, Zhang, et al. 2015a)
	4-Hydroxybenzaldehyde	27
	3′-Hydroxyacetophenone	28
	Scrokoelziside A	175
	Buergeriside A1	67
	Sibirioside A	68
	Cistanoside F	69
	Cistanoide D	43
	6′-O-Caffeoyl harpagide	106
	6′-O-E-p-Feruloyl harpagide	107
	6″-O-β-Glucopyranosylharpagoside	108
	8-O-Acetyl harpagide	100
	β-Sitosterol	192
	β-Sitosterol glucoside	193
	Angoroside C	46
	Nepitrin	3
	Buergerinin A	81
	Aucubin	109
	Ningpogenin	86
	Ningpogoside A	87
	Ningpogoside B	88
	4′-hydroxyacetophenone	30
	3′,5′-Dimethoxy-4′-hydroxyacetophenone	31
	3′-Methoxy-4′-hydroxyacetophenone	32
	(Z)-4-Hydroxycinnamic acid methyl ester	34
	(E)-p-Methoxycinnamic acid	11
	trans-Caffeic acid methyl ester	33
	Scropolioside B	135
	Scrophularianine A	164
	Scrophularianine B	165
	Scrophularianine C	166
	2,6-Dimethoxy-4-methoxymethylphenol	37
	Homovanillic alcohol	36
	Scrophuloside B4	117
	Scrophuloside A4	118
	6-O-Feruloylb-fructofuranosyl-(2→1)-O-α-glucopyranosyl-(6→1)-O-α-glucopyranoside	74
	Scrokoelziside B	176
	6-O-cinnamoyl b-fructofuranosyl-(2→1)-O-α-glucopyranosyl-(6→1)-O-α-glucopyranoside	73
	Ningposide A	61
	Ningposide B	62
	Homoplantaginin	9
	Eurostoside	115
	2-(3-Hydroxy-4-methoxyphenyl)ethyl-O-α-arabinopyranosyl-(1→6)-O-α-rhamnopyranosyl-(1→3)-O-β-Glucopyranoside	72
	PhenylO-β-xylopyranosyl-(1→6)-O-β-glucopyranoside	71
	Ningpoensines B/C	163
	Vanillin	29
	6-O-Methyl catalpol	94
	8- O-Feruloylharpagide	110
	8-O-(2-Hydroxycinnamoyl) harpagide	111
	6-O-α-D-Galactopyranosylharpagoside	112
	Harpagoside	113
	Harpagide	114
	Ningposide C	60
	Ningposide D	63
	Buergeriside C1	64
	Buergeriside B2	65
	Buergeriside B1	66
	Ningpoensine A	162
S. oxysepala	Scrokoelziside A	175	(Orangi et al. 2013, Orangi et al. 2016, Valiyari et al. 2012)
	Scrokoelziside B	176
	Verbascosaponin	177
	Harpagoside B	99
	Scropolioside D	131
	2-(4-chlorobenzyl amino) ethanol	167
	Eugenol	200
	Dehydroeugenol	201
	Methyl benzyl alcohol	202
	1-Octen-3-ol	204
S. nodosa	Jionoside D	50	(Miyase and Mimatsu 1999, Stevenson et al. 2002, Swiatek 1972)
	Scrovalentinoside	130
	Angoroside C	46
	Scrophuloside A2	120
	Scrophuloside A4	118
	Scrophuloside A5	121
	Scrophuloside A6	122
	Scrophuloside A7	123
	Scrophuloside A8	124
	Scrophuloside A1	119
	Buddlejoside A5	126
	Buddlejoside A3	127
	Buddlejoside A4	129
	Pulverulentoside II	125
	Scrophuloside A3	160
	Verbascoside A	128
	Scrophuloside B1	57
	Scrophuloside B2	58
	Purpureaside C	56
	Verbascoside	48
	Angoroside A	44
	cis-Verbascoside	59
S. scopolii	Angoroside A	44	(Calis et al. 1988a, Calis, et al. 1988b)
	Angoroside B	45
	Angoroside C	46
	Angoroside D	47
	Verbascoside	48
	Isoverbascoside	49
	ScropoliosideA	134
	ScropoliosideB	135
S. striata	Quercetin	1	(Monsef-Esfahani, et al. 2010)
	trans-cinnamic acid	11
	Isorhamnetin-3-O-rutinoside
	Nepitrin	3
	Verbascoside	48
	1-Octen-3-ol	204
S. scorodonia	8-O-Acetyl harpagide	100	(Emam et al. 1997, de Santos, et al. 2000, Bermejo, et al. 2002, Díaz, et al. 2004)
	Scrolepidoside	137
	Saikosapoinin I (Buddlejasaponin IV)	190
	Saikosapoinin II (Sandrosaponin I)	191
	Isoangoroside C	55
	Buddlejasaponin I	182
S. takesimensis	Isorhamnetin-3-O-rutinoside	2	(Kim, et al. 2012a)
	Nepitrin	3
	β-Sitosterol	192
	α-Spinasterol 3-O-β-D-glucopyranoside	194
	5-Hydroxypyrrolidin-2-one	168
	trans-Cinnamic acid	11
	(E)-p-Methoxycinnamic acid	12
	(E)-o-Methoxycinnamic acid	10
	Acacetin	5
S. trifoliata	Catalpol	93	(Ramunno et al. 2006)
	Aucubin	109

Table 3. Some of the Scrophularia species essential oil major compounds.

Species	Major compounds
S. oxysepala	Methyl benzaldehyde, methyl benzyl alcohol, 1-octen-3-ol, eugenol and phytol
S. amplexcaulis	Eugenol, 1-cten-3-ol, anethole, caryophyllene oxide and eugenol acetate
S. striata	1-octen-3-ol, banzyl banzoat, benzaldehyde, linalool and phytol
S. frigida	Oxygenated monoterpenes, L-linalool, geraniol, α-terpineol, and 1-octen-3-ol

Table 4. Pharmacological activities of some Scrophularia species.

Species	Biological activity	Responsible compound or extract	References
S. amplexicaulis	Antibacterial (aginest S. aureus)	Essential oil	Pasdaran et al. (2012, 2016)
	Antimalarial	Methanolic extract & fractions
	Free radical scavengering activities and general toxicity	Methanolic extract & fractions
S. dentata	Anti-inflammatory activity significantly inhibited CoA-induced splenocyte proliferation	Iridoids & Scrodentoids A–E, scropoliosides	Zhang et al. (2014, 2015b)
S. auriculata	Antibacterial	Phenolic acids	Cuéllar et al. (1998) and Giner et al. (2000)
	Anti-inflammatory	Iridoids and saponins, Hydroalcoholic extract
S. buergeriana	Neuroprotective & Anti-amnestic	Chloroformic & methanolic extracts from roots, harpagoside and 8-O-E-p-methoxycinnamoylharpagide Phenylpropanoids & Phenolic acids	Kim and Kim (2000), Lee et al. (2002), Kim et al. (2003b), Jeong et al. (2008), and Kim et al. (2011, 2012b)
	Hepatoprotective
	Anti-inflammatory
S. canina	Insecticidal activity	Plant, phenolic acids	Germinara et al. (2011)
S. cryptophila	Antiprotozoal and antimycobacterial activities	Crypthophilic acid A, C & buddlejasaponin III, acetylharpagide	Tasdemir et al. (2008)
S. deserti	inhibiting an enzyme or enzymes of Type II fatty acid synthesis (FAS)	Unsaturated fatty acids, ethanolic extract	Ahmed et al. (2003), Stavri et al. (2006) and Bahmani et al. (2013)
	Anti-inflammatory	Scropolioside-D2 & harpagoside B
	Antidiabetic	Scropolioside-D2 & harpagoside B
S. frutescens	Antibacterial	Aerial part aqueous extract, phenolic acids	Fernandez et al. (1996, 1998) and Garcia et al. (1998)
	Anti-inflammatory	Phenolic acids, Iridoids
	Cytostatic activity	Phenolic acids
S. grossheimi	Hepatoprotective	1,6-di-O-caffeoyl-β-D-glucopyranose & flavonoids	Akhmadov et al. (1969), Akhmedov and Litvinenko (1969) and Galindez et al. (2001)
S. koelzii	Hepatoprotective & immunostimulant	Scropolioside-A, koelzioside, harpagoside, 6-O-(3″-O-p-Methoxy-cinnamoyl)-α-L-rhmanopyranosyl catalpol, chloroform fraction of the aerial parts	Garg et al. (1994)
S. lepidota	Anti-protozoal & Antiplasmodial	Ningpogenin, sinuatol	Tasdemir et al. (2005)
S. ningpoensis	Cardioprotective	Trans-caffeic acid methyl ester & 4-methylcatechol, 6″-O-caffeoylharpagide, 6″-O-(p-coumaroyl) harpagide, harpagoside and Phenylethanoide glycosides	Chen et al. (2008) and Zhu et al. (2013)
	Anti-inflammatory	Ningpogenin, ningpogoside A and ningpogoside B and hydrophilic extract	Qian et al. (1991)
	Antibacterial	Scrokoelziside A and ethanolic leave extract	Li et al. (2009)
S. nodosa	Wound healing activity	Scopolioside A, scrophuloside A4 and scrovalentinoside	Stevenson et al. (2002)
S. oxysepala	Insecticidal activity	Essential oil, methanolic fractions	Pasdaran et al. (2013, 2017) and
	Apoptosis	Dichloromethane and methanol extracts	Valiyari et al. (2012) and Orangi et al. (2013)
	Cytotoxic Free radical scavenging	Methanolic fractions, scropolioside D, harpagoside B &2-(4-chlorobenzyl amino) ethanol	Pasdaran et al. (2017)
S. striata	Wound healing and Anti-inflammatory	Ethanolic extract, ethyl acetate extract	Hajiaghaee et al. (2007) and Azadmehr et al. (2009)
	Antibacterial	Ethanolic extract	Benito et al. (1998) and Bahrami and Ali (2010)
	Antioxidant	Ethanolic extract	Díaz et al. (2004)
S. scorodonia	Anti-inflammatory	Angoroside A, angoroside C, angoroside D, acteoside, isoacteoside, Buddlejasaponin I& Saikosapoinin I, II
	Antiviral	Scorodioside, Buddlejasaponin IV	Bermejo et al. (2002)
S. takesimensis	Strong aldose reductase (AR) inhibitory activity	Acacetin	Kim et al. (2012a)

Figure 2. Isolated flavonoids and flavonoid glycosides from Scrophularia genus.

Figure 3. Phenolic acids compounds reported from Scrophularia plants.

Figure 4. Phenylethanoid glycosides isolated from Scrophularia plants.

Figure 5. Chemical structures of Scrophularia glycoside esters.

Figure 6. Chemical structures of Scrophularia C₉ iridioides.

Figure 8. Alkaloids, resin glycosides and fatty acids derivatives of Scrophularia plants.

Figure 10. Diterpenoids and some of the essential oil major compositions of Scrophularia species.

Figure 11. Studies on biological actives of Scrophularia spp. phytochemicals.

Figure 12. The ratio of biological activities reported for Scrophularia spp.

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