A comprehensive review on phytochemistry, pharmacology, and flavonoid biosynthesis of Scutellaria baicalensis

Figures & data

Figure 1. Pictures of the plant (A), TCM crude drugs (B), and TCM prepared slices (C) of Scutellaria baicalensis.

Table 1. Compounds 1-126 from Scutellaria baicalensis.

No.	Name	Molecular formula	Molecular weight	Plant part	References
Free flavonoids
1	Baicalein (5,6,7-Trihydroxyflavone)	C15H10O5	270	Root; Hairy root	Popova et al. 1973;Ji et al. 2015; Zhou et al. 1997
2	5,6-Dihydroxy-7-methoxyflavone	C16H12O5	284	Root	Popova et al. 1973
3	Scutellarein (5,6,7,4'-Tetrahydroxyflavone)	C15H10O6	286	Root	Wang 2002
4	5,6,7-Trihydroxy-4'-methoxyflavone	C16H12O6	300	Root	Wang 2002
5	Oroxylin A (5,7-Dihydroxy-6-methoxyflavone)	C16H12O5	284	Root	Popova et al. 1973; Ji et al. 2015
6	Tenaxin II (5,7,2'-Trihydroxy-6-methoxyflavone)	C16H12O6	300	Root	Tomimori et al. 1983
7	5,7,4'-Trihydroxy-6-methoxyflavone	C16H12O6	300	Aerial part	Ma 2013
8	5,7-Dihydroxy-6,8-dimethoxyflavone	C17H14O6	314	Root	Wang 2002
9	5,7,2'-Trihydroxy-6,8-dimethoxyflavone	C17H14O7	330	Root	Wang 2002
10	5,8-Dihydroxy-6,7-dimethoxyflavone	C17H14O6	314	Root	Tomimori et al. 1982
11	5,8,2'-Trihydroxy-6,7-dimethoxyflavone	C17H14O7	330	Root	Takagi et al. 1980
12	Tenaxin I (5,2'-Dihydroxy-6,7,8-trimethoxyflavone)	C18H16O7	344	Root	Tomimori et al. 1983; Xu DY et al. 2011
13	5,2',5'-Trihydroxy-6,7,8-trimethoxyflavone	C18H16O8	360	Root	Tomimori et al. 1984a
14	Skullcapflavone II (5,6'-Dihydroxy-6,7,8,2'-tetramethoxyflavone)	C19H18O8	374	Root; Hairy root	Ishimaru et al. 1995; Zhou et al. 1997
15	5,4'-Dihydroxy-6,7,3',5'-tetramethoxyflavone	C19H18O8	374	Aerial part	Ma 2013
16	5,2'-Dihydroxy-6,7,8,3'-tetramethoxyflavone	C19H18O8	374	Hairy root	Nishikawa et al. 1999
17	Chrysin (5,7-Dihydroxyflavone)	C15H10O4	254	Root; Aerial part; Hairy root	Takagi et al.1980; Ma 2013; Zhou et al. 1997
18	Norwogonin (5,7,8-Trihydroxyflavone)	C15H10O5	270	Root	Popova et al. 1973; Tomimori et al. 1983
19	Isoscutellarein (5,7,8,4'-Tetrahydroxyflavone)	C15H10O6	286	Aerial part	Ma 2013
20	Apigenin (5,7,4'-Trihydroxyflavone)	C15H10O5	270	Root; Aerial part	Wang 2002; Ma 2013
21	4'-Hydroxywogonin(5,7,4'-Trihydroxy-8-methoxyflavone)	C16H12O6	300	Root	Tomimori. et al. 1982; Wang 2002
22	2'-Hydroxychrysin (5,7,2'-Trihydroxyflavone)	C15H10O5	270	Root	Tomimori et al. 1984a
23	5,7,2',3'-Tetrahydroxyflavone	C15H10O6	286	Root	Tomimori et al. 1984b
24	5,7,2',5'-Tetrahydroxyflavone	C15H10O6	286	Root	Zhang et al. 1994
25	5,7,2',6'-Tetrahydroxyflavone	C15H10O6	286	Root	Tomimori et al. 1982; Ishimaru et al. 1995
26	5,7,6'-Trihydroxy-2'-methoxyflavone	C16H12O6	300	Root	Tomimori et al. 1984a
27	Wogonin (5,7-Dihydroxy-8-methoxyflavone)	C16H12O5	284	Root; Aerial part; Hairy root	Popova et al. 1973; Ma 2013; Zhou et al. 1997
28	Scutevulin (5,7,2'-Trihydroxy-8-methoxyflavone)	C16H12O6	300	Root	Tomimori et al. 1984a
29	5,7,6'-Trihydroxy-8,2'-dimethoxyflavone	C17H14O7	330	Root	Tomimori et al. 1984a
30	Viscidulin III (5,7,3',6'-Tetrahydroxy-8,2'-dimethoxyflavone)	C17H14O8	346	Root	Tomimori et al. 1984a; Zhang et al. 1994
31	5,7-Dihydroxy-8,2',3',6'-tetramethoxyflavone	C19H18O8	374	Root	Long et al. 2015
32	7-Methoxychrysin (5-Hydroxy-7-methoxyflavone)	C16H12O4	268	Aerial part	Wang HW et al. 2016
33	5,8-Dihydroxy-7-methoxyflavone	C16H12O5	284	Root	Popova et al. 1973
34	Genkwanin (5,4'-Dihydroxy-7-methoxyflavone)	C16H12O5	284	Aerial part	Wang HW et al. 2016
35	5,8,2'-Trihydroxy-7-methoxyflavone	C16H12O6	300	Root	Takagi et al. 1980
36	7-O-Methylwogonin (5-Hydroxy-7,8-dimethoxyflavone)	C17H14O5	298	Root	Tomimori et al. 1983
37	Skullcapflavone I (5,2'-Dihydroxy-7,8-dimethoxyflavone)	C17H14O6	314	Root; Hairy root	Takido et al. 1979; Zhou et al. 1997
38	Viscidulin II (5,2',6'-Trihydroxy-7,8-dimethoxyflavone)	C17H14O7	330	Root	Tomimori et al. 1984a
39	Rivularin (5,6'-Dihydroxy-7,8,2'-trimethoxyflavone)	C18H16O7	344	Root; Hairy root	Zhang et al. 1994; Zhou et al. 1997
40	6'-Hydroxy-5,6,7,8,2'-pentamethoxyflavone	C20H20O8	388	Root	Wang 2002
41	6,6'-Dihydroxy-5,7,8,2'-tetramethoxyflavone	C19H18O8	374	Root	Wang 2002
42	5,7,3',4',5'-Pentamethoxyflavone	C20H20O7	372	Aerial part	Wang HW et al. 2016
43	Viscidulin І (5,7,2',6'-Tetrahydroxyflavonol)	C15H10O7	302	Root	Tomimori et al. 1984a;Ji et al. 2015
44	5,7,6'-Trihydroxy-2'-methoxyflavonol	C16H12O7	316	Root	Long et al. 2015
45	Isocarthamidin ((2S)-5,7,8,4'-Tetrahydroxyflavanone)	C15H12O6	288	Leaf; Root	Takido et al. 1976; Wang 2002
46	Carthamidin ((2S)-5,6,7,4'-Tetrahydroxyflavanone)	C15H12O6	288	Leaf; Root	Takido et al. 1976; Wang 2002
47	(2S)-5,7,4'-Trihydroxy-6-methoxyflavanone	C16H14O6	302	Root	Takagi et al1980
48	(+)-Eriodictyol ((2S)-5,7,3',4'-Tetrahydroxyflavanone)	C15H12O6	288	Root	Zhang et al. 1994
49	(2S)-5,4'-Dihydroxy-7-methoxyflavanone	C16H14O5	286	Aerial part	Wang HW et al. 2016
50	DihydrooroxylinA ((2S)-5,7-Dihydroxy-6-methoxyflavanone)	C16H14O5	286	Root	Takagi et al. 1980; Xu DY et al. 2011
51	(2S)-7-Hydroxy-5-methoxyflavanone	C16H14O4	270	Root	Xu DY et al. 2011
52	(2S)-5,7,2',6'-Tetrahydroxyflavanone	C15H12O6	288	Root	Kubo et al. 1981
53	(2S)-7,2',6'-Trihydroxy-5-methoxyflavanone	C16H14O6	302	Root	Tomimori et al. 1984a
54	(2R,3R)-3,5,7,2',6'-Pentahydroxyflavanone	C15H12O7	304	Root	Takagi et al. 1981b; Ji et al. 2015
55	2,6,2',4'-Tetrahydroxy-6'-methoxychalcone	C16H14O6	302	Root	Tomimori et al. 1984a
56	8,8''-Bibaicalein	C30H18O10	538	Root	Wang 2002
Flavonoid glycosides
57	Apigenin 7-O-β-D-glucoside	C21H20O10	432	Aerial part	Ma 2013
58	Baicalein 7-O-β-D-glucoside	C21H20O10	432	Root; Aerial part	Tomimori et al. 1984a; Ma 2013
59	Oroxylin A 7-O-β-D-glucoside	C22H22O10	446	Aerial part; Root	Ma 2013; Ji et al. 2015
60	5,6'-Dihydroxy-7,8-dimethoxyflavone 2'-O-β-D-glucoside	C23H24O12	492	Root; Hairy root	Miyaichi et al. 1995; Zhou et al. 1997
61	5,6'-Dihydroxy-6,7,8-trimethoxyflavone 2'-O-β-D-glucoside	C24H26O13	522	Root	Ishimaru et al. 1995
62	5,6'-Dihydroxy-6,7-dimethoxyflavone 2'-O-β-D-glucoside	C23H24O12	492	Root; Hairy root	Ishimaru et al. 1995; Zhou et al. 1997
63	5,7,6'-Trihydroxyflavone 2'-O-β-D-glucoside	C21H20O11	448	Hairy root	Zhou et al. 1997
64	Viscidulin III 6'-O-β-D-glucoside	C23H24O13	508	Root; Hairy root	Zhang et al. 1994; Zhou et al. 1997
65	Wogonin 5-O-β-D-glucoside	C22H22O10	446	Root	Takagi et al. 1981b; Ji et al. 2015
66	3,5,7,6'-Tetrahydroxyflavone 2'-O-β-D-glucoside	C21H20O12	464	Root	Miyaichi et al. 1995
67	Kaempferol 3-O-β-D-glucoside	C21H20O11	448	Aerial part	Cha et al. 2006
68	5,6,8-Trimethoxy-3',4'-methylenedioxyflavone 7-O-β-D-glucoside	C26H28O12	532	Root	Lin et al. 2013
69	3,5,8-Trimethoxy-3',4'-methylenedioxyflavone 7-O-β-D-glucoside	C26H28O12	532	Root	Lin et al. 2013
70	(2S)-5-Hydroxy-6-methoxyflavanone 7-O-β-D-glucoside	C22H24O10	448	Root	Miyaichi et al. 1995
71	(2S)-5,7,6'-Trihydroxyflavanone 2'-O-β-D-glucoside	C21H22O11	450	Root	Ji et al. 2015
72	Delphinidin 3-O-(6-O-malonyl)-β-D-glucoside-5-O-β-D-glucoside	C30H33O20	713	Flower	Oszmianski et al. 2004
73	Chrysin 7-O-β-D-glucuronide	C21H18O10	430	Root; Aerial part; Root	Miyaichi et al. 1994; Ma 2013; Ji et al. 2015
74	Baicalin (5,6-Dihydroxyflavone 7-O-β-D-glucuronide)	C21H18O11	446	Root; Aerial part; Hairy root	Shibata et al. 1923; Ishimaru et al. 1995; Ma 2013; Zhou et al. 1997
75	5,2'-Dihydroxy-6-methoxyflavone 7-O-β-D-glucuronide	C22H20O12	476	Root	Miyaichi et al. 1994
76	Wogonoside (Wogonin 7-O-β-D-glucuronide)	C22H20O11	460	Root; Hairy root	Ishimaru et al. 1995;Ji et al. 2015; Zhou et al. 1997
77	Oroxyloside (Oroxylin A 7-O-β-D-glucuronide)	C22H20O11	460	Root	Zhang et al. 1997
78	Norwogonin 7-O-β-D-glucuronide (5,8-dihydroxyflavone 7-O-β-D-glucuronide)	C21H18O11	446	Root	Ji et al. 2015
79	Isoscutellarein 8-O-β-D-glucuronide	C24H24O12	504	Leaf	Nagai et al. 1989
80	5-Hydroxy-7,8,6'-trimethoxyflavone 2'-O-β-D-glucuronide	C24H24O13	520	Hairy root	Zhou et al. 1997
81	Scutellarin	C21H18O12	462	Root	Ji et al. 2015
82	Apigenin 7-O-β-D-glucuronide	C21H18O11	446	Aerial part	Cha et al. 2006
83	Patuletin 7-O-β-D-glucuronide (3,5,3',4'-Tetrahydroxy- 6-methoxyflavone 7-O-β-D-glucuronide)	C22H20O14	508	Root	Lin et al. 2013
84	Dihydrobaicalin ((2S)-5,6-Dihydroxyflavanone 7-O-β-D-glucuronide)	C21H20O11	448	Root	Tomimori et al. 1983
85	(2S)-5-Hydroxy-6-methoxyflavanone 7-O-β-D-glucuronide	C22H22O11	462	Root	Ji et al. 2015
86	(2S)-5,6,3',4'-Tetrahydroxyflavanone 7-O-β-D-glucuronide	C21H20O13	480	Aerial part	Liu et al. 2011
87	Isocarthamidin 7-O-β-D-glucuronide ((2S)-5,8,4'-Trihydroxyflavanone 7-O-β-D-glucuronide)	C21H20O12	464	Aerial part	Liu et al. 2011;Wang HW et al. 2016
88	Carthamidin 7-O-β-D-glucuronide (Dihydroscutellarein 7-O-β-D-glucuronide, Scutellarin B)	C21H20O12	464	Aerial part	Liu et al. 2011
89	(2S)-5,8,3',4'-Tetrahydroxyflavanone 7-O-β-D-glucuronide	C21H20O13	480	Aerial part	Liu et al. 2011
90	Chrysin 8-C-β-D-glucoside	C21H20O9	416	Root	Miyaich et al. 1994; Ji et al. 2015
91	Chrysin 6-C-β-D-glucoside	C21H20O9	416	Root	Miyaichi et al. 1994
92	Chrysin 6-C-β-D-glucoside-8-C-α-L-arabinopyranoside	C26H28O13	548	Root; Hairy root	Takagi et al. 1981a;Ji et al. 2015; Zhou et al. 1997
93	Chrysin 6-C-α-L-arabinopyranoside-8-C-β-D-glucoside	C26H28O13	548	Root; Hairy root	Takagi et al. 1981a; Ji et al. 2015; Zhou et al. 1997
94	Chrysin 6-C-β-L-arabinopyranoside-8-C-β-D-glucoside	C26H28O13	548	Root	Liu 2008
95	Chrysin 6-C-β-D-glucoside-8-C-β-L-arabinopyranoside	C26H28O13	548	Root	Liu 2008
96	Chrysin 6-C-β-arabinofuranoside-8-C-β-D-glucoside	C26H28O13	548	Root	Liu 2008
97	Chrysin 6-C-β-D-glucoside-8-C-β-arabinofuranoside	C26H28O13	548	Root	Liu 2008
98	Chrysin 3-C-α-arabinopyranoside-8-C-β-D-glucoside	C26H28O13	548	Root	Lin et al. 2013
99	Apigenin 6-C-α-L-arabinopyranoside-8-C-β-D-glucoside (isoschaftoside)	C26H28O14	564	Aerial part	Cha et al. 2006
100	(2R,3R)-Pinobankasin 6-C-glucoside-8-C-arabinopyranoside	C26H30O14	566	Root	Lin et al. 2013
Phenylethanoid glycosides
101	Salidroside (4-Hydroxy-β-phenylethyl-β-D-glucoside)	C14H20O7	300	Hairy root	Zhou et al. 1997
102	Darendoside B	C21H32O12	476	Root	Miyaichi et al. 1995
103	Martynoside (2-(3-Hydroxy-4-methoxyphenyl) ethyl-1-O-α-L-rhamnosyl(1→3)-β-D-(4-feruloyl)-glucoside)	C31H40O15	652	Hairy root; Root	Zhou et al. 1997; Takagi et al. 1981b
104	Acteoside	C29H36O15	624	Hairy root; Root	Zhou et al. 1997; Miyaichi et al. 1994;Ji et al. 2015
105	Isomartynoside	C31H40O15	652	Root	Miyaichi et al. 1994
106	Leucosceptoside A	C30H38O15	638	Hairy root; Root	Zhou et al. 1997; Miyaichi et al. 1994
107	Cistanoside D	C31H40O15	652	Root	Ji et al. 2015
108	Darendoside A	C19H28O11	432	Root	Miyaichi et al. 1995
Others
109	Stigmasterol	C29H48O	412	Root	Wang 2002
110	β-Sitosterol	C29H50O	414	Root	Xu DY et al. 2011
111	Daucosterin	C35H60O6	576	Root	Wang 2002
112	Scutebaicalin	C34H38O7	558	Aerial part	Hussein et al. 1996
113	Pellitorine	C14H25NO	223	Root	Xu et al. 2016
114	(E)-4-[(2-methylpropyl) amino]-4-oxo-2-butenoic acid	C8H13NO3	171	Root	Xu et al. 2016
115	Dihydropiperlonguminine	C16H21NO3	275	Root	Xu et al. 2016
116	Futoamide	C18H23NO3	301	Root	Xu et al. 2016
117	Piperlonguminine	C16H19NO3	273	Root	Xu et al. 2016
118	Benzoic acid	C7H6O2	122	Root	Xu DY et al. 2011
119	Phenyl acetic acid	C8H8O2	136	Root	Liu YX et al. 2009
120	Syringaldehyde	C9H10O4	182	Root	Xu et al. 2016
121	4-O-β-D-glucosyl-trans-p-coumaric acid	C15H18O8	326	Root	Liu YX et al. 2009
122	Ferulic acid methyl ester	C11H12O4	208	Root	Xu et al. 2016
123	4-O-β-D-glucosyl-cis-p-coumaric acid	C15H18O8	326	Root	Liu YX et al. 2009
124	Vanillin	C8H8O3	152	Root	Xu et al. 2016
125	(+)-Crotepoxide	C18H18O8	362	Root	Xu et al. 2016
126	(+)-Syringaresinol-O-β-D-glucoside	C28H36O13	580	Root	Miyaichi et al. 1994

Figure 3. UPLC/UV chromatograms (275 nm) for quantitative analysis of 12 major compounds in Scutellaria baicalensis (Huang-Qin crude drugs). 1, baicalein; 5, oroxylin A; 27, wogonin; 54, (2R,3R)-3,5,7,2′,6′-pentahydroxyflavanone; 74, baicalin; 76, wogonoside; 77, oroxylinA 7-O-β-D-glucuronoside; 78, norwogonin 7-O-β-D-glucuronoside; 81, scutellarin; 92, chrysin 6-C-β-D-glucoside-8-C-α-L-arabinopyranoside; 93, chrysin 6-C-α-L-arabinopyranoside-8-C-β-D-glucoside; 104, acteoside (Adapted from Ji et al. 2015).

Figure 4. Screening of 28 compounds from Scutellaria baicalensis for their anti-H1N1 viral, cytotoxic, and Nrf2 activation activities. For compounds identification, see Table 1 (Adapted from Ji et al. 2015).

Table 2. The anti-tumor activities of Scutellaria baicalensis and its compounds.

Drugs	Dose	Model	Efficacy	Mechanism	References
Water extract	20–800 μg/mL	HepG2 liver cancer cells	IC50, 360 μg/mL	G2/M phase arrest	Ye et al. 2009
Water extract	10–500 μg/mL	A549 lung cancer cells	Inhibited cell motility at >250 μg/mL	Inhibition of MMP-2 activity and cell motility	Park et al. 2011
Water extract	40–800 μg/mL 200 mg/kg five times per week for 7 weeks i.g.	Prostate cancer cell lines (LNCaP, PC-3); PC-3 prostate cancer xenograft NCR nude mice	IC50, 100–150 μg/mL; Tumor inhibition rate, 50%	Inhibition of COX-2 activity; G1 and G2/M phase arrest	Ye F et al. 2007
Water extract	1.5–1500 μg/mL 75 mg/kg five times/week for 7 weeks, p.o.	Head and neck squamous cell carcinoma (SCC-25, KB); KB HNSCC xenograft female NCR/NU nude mice	IC50, 150 μg/mL; Tumor inhibition rate, 66%	Inhibition of PGE2 synthesis via suppression of COX-2 expression	Zhang et al. 2003
Methanol extract	400 μg/mL	HepG2 liver cancer cells	Inhibition rate, 44.4%	Regulation of MMP-2 and FOXM1 activities	Park et al. 2014
Ethanol extract	7.8–250 μg/mL	Lung cancer cell lines (A549, SK-LU-1, SK-MES-1)	IC50, 57.2–102.1 μg/mL	S and G0/G1 phase arrest; increased expression of p53 and Bax	Gao et al. 2011
Ethanol extract	0–100 μg/mL	Cell lines derived from primary and recurrent brain tumors from patients	IC50, 50–100 μg/mL; Increasing inhibitory effect with anti-tumor drug BCNU		Scheck et al 2006
Total free flavonoid extract	25 and 100 mg/kg for 30 d, p.o.	A549 human lung cancer xenograft female BALB/c nude mice	Tumor inhibition rate, 25.5%	S phase arrest; inhibition of DNA synthesis	Wang Y et al. 2016
Fraction (containing baicalein and wogonin)	1–100 μg/mL	MCF-7 breast cancer cells	Inhibition rate, 81.6% at 100 μg/mL	S-phase and G2/M-phase arrest; increasing cell apoptosis	Wang et al. 2010
Extracts	10^-3–10^3 μg/mL	Myeloid leukemia cells (HL-60, NB-4, THP-1, U937), lymphocytic leukemia cells (Blin-1, Nalm-6), lymphoma cell lines (Daudi, Raji, Ramos, NCEB1), myeloma cell lines (NCIH929, U266)	IC50, 4.57–12.3 μg/mL	Modulation of the Bcl family of genes and mitochondrial damage	Kumagai et al. 2007
Baicalin	25–800 μM	Prostate cancer cell lines (DU145, PC-3, LNCaPFGC, CA-HPV-10)	Cytotoxic for several human prostatic cancer cell lines; IC50, 150 μM for DU145 cells	Induction of apoptosis	Chan et al. 2000
Baicalin	3.2–320 μg/mL; 50, 100, 200 mg/kg five times/week for 2 weeks, i.p.	Mc3 mucoepidermoid carcinoma cells; Mc3 mucoepidermoid carcinoma xenograft BALB/c nude mice	IC50, 40 μg/mL; Tumor inhibition rate, about 50% at high dose	G0/G1 and G2/M phase arrest; decreasing the mitochondrial membrane potential	Xu XF et al. 2011
Baicalein	20 mg/kg/d for 2 weeks p.o.	LnCaP 35 prostate cancer xenograft BALB/c nude mice	Tumor inhibition rate, 55%	Reduce expression of the androgen receptor and androgen-regulated genes	Bonham et al. 2005
Baicalein	0–100 μM; 0.8 mg/mouse for 9 times for 21 d, i.p.	5637 bladder tumor cells; MB49 bladder cancer xenograft female C57BL/6 mice	G1 phase and S phase arrest at <100 μM	G1 and S phase arrest; inhibition of AKT, GSK3β, ERK, p38, and p65NF-κB, p65NF-κB	Wu et al. 2013
Baicalein	50–400 μM	Head and neck squamous cell carcinoma (SCC-25, KB)	IC50, 75 μM	Inhibition of PGE2 synthesis via suppression of COX-2 expression	Zhang et al. 2003
Baicalein	0–60 μM; 15 and 50 mg/kg/day for 1 week, i.g.	SGC-7901 gastric cancer cells; SGC-7901 gastric cancer xenograft BALB/c nude mice	IC50, about 30 μM; Tumor inhibition rate, about 50% at high dose	S phase arrest; Inducing apoptosis through the mitochondrial pathway	Mu et al. 2016
Baicalein	20–100 μM; 30 mg/kg/2 d for 4 weeks, i.p.	HCT-116 human colorectal cancer cells; HCT-116 human colorectal cancer xenograft nude mice	IC50, 40.1 μM; Tumor inhibition rate, about 50%	S phase arrest and pro-apoptotic effects; inducing the activation of caspase 3 and 9	Wang CZ et al. 2015
Baicalein	7–56 μM	HSC-3 oral cancer cells	IC50, ∼50 μM	G1 phase arrest; enhancing the degradation of cyclin D1 and activating AhR to decrease Rb phosphorylation	Cheng YH et al. 2012
Wogonin	1–100 μM	GBC-SD human gallbladder carcinoma cells	IC50, ∼50 μM	Inhibiting cell mobility and invasion by upregulating the metastasis suppressor maspin	Dong et al. 2011
Wogonin	0.1, 1, 10 mg/kg	T47D or MDA-MB-231 breat cancer xenograft female nude BALB/c mice	Tumor inhibition rate, 88% at high dose	Downregulation of the Akt-dependent canonical Wnt signaling pathway and p27^kip pathway; downregulation of ERa and c-ErbB2	Chung et al. 2008
Baicalin, wogonin, baicalein		Leukemia cell lines (CCRF-CEM, K562, P3HR-1, Raji, U937)	IC50, 10.6-20.5 μg/mL	Cellular DNA fragmentizing and G0/G1 phase arrest	Shieh et al. 2006
Wogonin, water extract	10–100 μM; 0.5–3 mg/mL	HL-60 leukemia cells	IC50, ∼50 μM (wogonin); ∼1 mg/mL (extracts)	Induction of Bax/Bcl-2 apoptosis and telomerase inhibition suppression of c-myc	Huang et al. 2010
Wogonoside	80 mg/kg/2 d for 14 d, i.p.	U937 acute myeloid leukemia xenograft BALB/c nude mice	Tumor inhibition rate, 41%	Cell cycle arrest and differentiation by affecting expression and subcellular localization of PLSCR1	Chen et al. 2013

Table 3. The neuroprotective activities of Scutellaria baicalensis and its compounds.

Drugs	Dose	Experimental model	Efficacy	Mechanism	References
Methanol extract	0.1–1mg/kg for 7 d, i.p.	Global cerebral ischemia Wistar rats	89.6% protection of neuronal cell density	Inhibiting proinflammatory events (TNF-αand NO) and oxidative stress	Kim et al. 2001
Ethanol extract	1–100 μg/mL	Glutamate- and NMDA-induced primary rat cortical cell excitotoxicity	Protection rate, 90–95% at high dose	Inhibition of NMDA receptor function by interacting with the glycine binding site of the NMDA receptor	Yang J et al. 2014
Water extract	50 μg/mL	H2O2-induced neuronal HT-22 cell injury	Protection rate, 80–90%	Increasing the Bcl-2 level and decreasing the Bax level	Choi et al. 2002
Stem and leave extracts	18–76 μg/mL	H2O2-induced PC12 cell injury	Protection rate, >90% at high dose	Elevating the activity of SOD and Na^+-K^+-ATPase and lowering the MDA level and LDH release	Shang et al. 2006
Stem-leaf total flavonoids	50, 100 mg/kg for 60 d, i.p.	Chronic cerebral ischemia-induced vascular dementia of SD rats	Improving spatial learning and memory at high dose	Regulating kinases-triggered phosphorylation and PP2A-catalyzed dephosphorylation	Cao et al. 2016
Stem-leaf total flavonoids	5 mg/kg for 5 d, i.v.	MPTP-induced Parkinson's disease in C57BL/6J mice	Higher Hanging test scores; improving the behaviors and the numbers of dopaminergic neurons in the substantia nigra	Reduction in serum malondialdehyde and inhibition of oxidation, alleviating the damage of oxygen free radicals to dopaminergic neurons	Li et al. 2016
Wogonin	1–300 μg/mL	Glutamate, N-methyl-D-aspartic acid, H2O2, xanthine/xanthine oxidase, BSO, Fe^2+ and L-ascorbic acid induced primary rarat cortical cell toxicity	EC50, 6.8–143.3 μg/mL	Radical scavenging	Cho and Lee 2004
Baicalein	1–5 μM	LPS-induced primary rat embryo midbrain neuron-glia damage	Attenuating LPS-induced decrease in dopamine uptake and loss of TH-immunoreactive neurons	Inhibition of LPS-induced production of NO and free radicals from microglia	Li et al. 2005
Baicalein	200 mg/kg for a week, i.p.	MPTP-induced Parkinson's disease in C57BL/6J mice	Improving the abnormal behavior	Increasing the levels of DA and 5-HT in the striatum and the counts of dopaminergic neurons, inhibiting oxidative stress and the astroglia response	Cheng et al. 2008
Baicalein	200 mg/kg for 3 weeks, i.p.	6-Hydroxydopamin-induced experimental parkinsonism SD rats	Decreasing the burst frequency and amplitude of muscle activity to 13.43% and 35.18%	Increasing the number of dopaminergic neurons related with anti-apoptotic, pro-differentiation and anti-inflammatory action	Mu et al. 2009
Baicalein	10–50 μM	Thapsigargin and brefeldin A-induced HT22 mouse hippocampal neuronal cells	Attenuating sub-G1 fractions from 55.27–63.84% to 26.20–28.96%	Reducing CHOP induction and ROS accumulation and mitochondrial damage.	Choi et al. 2010
Baicalein	1, 2 and 4 mg/kg for 1 time (acute) and 21 d (chronic), i.p.	Acute and chronic depression rats	Reducing the immobility time in the forced swimming test and tail suspending test	Hippocampal ERK-mediated neurotrophic action	Xiong et al. 2011
Baicalein	1–30 μM	α-syn-Oligomer-induced SH-SY5Y cell toxicity, Aβ fibril-induced PC12 cells toxicity	Protection rate, 62–80%	Inhibiting formation of α-synuclein pligomers within living cells and prevents Aβ peptide fibrillation and oligomerization	Lu et al. 2011
Baicalein	140, 280 mg/kg for 7 d, i.g.	MPTP-induced Parkinson's disease in mice	Shortening the total time for climbing down the pole, prolonging the latent periods of rotarod, and increasing the vertical movements	Regulation of genes such as LIMK1, SNCA and GLRA1	Gao et al. 2015
Baicalein	1 mg/kg pretreated for 2 (1st and 4th) or 4 times, i.p.	Methamphetamine-induced amnesia in ICR mice	Attenuating memory deficits and oxidative hippocampal damage		Wong et al. 2014
Baicalein	200, 400 mg/kg for 28 d, p.o.	Rotenone-induced Parkinson's disease in SD rats	Attenuating behavioral impairments and the depletion of dopaminergic neurons; restoring mitochondrial function and improved mitobiogenesis	Through the cAMP-responsive element binding protein (CREB) and glycogen synthase kinase-3β (GSK-3β) pathways	Zhang X et al. 2017a
Baicalein	200, 400 mg/kg for 28 d, p.o.	Rotenone-induced Parkinsonian SD rats	Improving motor impairments, attenuateing brain damage, suppressing the production of proinflammatory cytokines, modulating the astrocytes and microglia activation	Through anti-neuroinflammation	Zhang X et al. 2017b
Baicalein	30 mg/kg for 4 d, i.p.	Acrolein-induced Parkinsonian SD rats	Attenuating oxidative stress and protein conjugation and inhibiting inflammation in the nigrostriatal dopaminergic	Inhibiting oxidative stress, protein conjugation, and inflammation	Zhao WZ et al. 2018
Baicalin	1–100 μM	Prolyl oligopeptidase	IC50, 12 μM		Tarragó et al. 2008
Baicalin	0–10 μM	Aβ 1–42-induced SH-SY5Y cell injury	Protecting cells viability from 57% to 78% at high dose	Inhibiting Aβ 1–42 aggregation and reducing H2O2-mediated oxidative stress and damage	Yin et al. 2011
Baicalin	100, 200 mg/kg for 7 d, i.p.	Transient global cerebral ischemic-reperfusion injury in Mongolian gerbils	Attenuating ischemia-induced neuronal cell damage	Related with anti-oxidative and anti-apoptotic properties	Cao et al. 2011
Baicalin	100 mg/kg of twice /day for 7 d, i.g.	Global cerebral ischemia/reperfusion rats	Improving the learning and memory	Inhibition of COX-2 expression	Cheng OM et al. 2012
Baicalin	200 mg/kg/day for 7 d, i.g.	Transient global cerebral ischemia Mongolian gerbils	Facilitating neurological function, suppressing the ischemia-induced neuronal damage	Activating GABAergic signaling, HSP70 and MAPKs cascades in global ischemia	Dai et al. 2013

Figure 5. Different biosynthesis pathways in roots and aerial parts of Scutellaria baicalensis.

Figure 6. Key amino acid residues for the catalytic selectivities of O-glucuronyltransferases and O-glycosyltransferases (Adapted from Noguchi et al. 2009).

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