This paper explored the ecologically suitable areas for growing Scutellaria baicalensis using Geographic Information System for Global Medicinal Plants(GMPGIS), to figure out the resource distribution of S. baicalensis worldwide and provide a scientific basis for its scientific introduction. A total of 349 S. baicalensis sampling sites were selected all over the world for GMPGIS-based analy-sis of the ecologically suitable areas with six ecological factors including annual average temperature, average temperature during the coldest season, average temperature during the warmest season, average annual precipitation, average annual relative humidity, and annual average illumination and soil type as the ecological indexes. The results demonstrated that the ecologically suitable areas for growing S. baicalensis were mostly located in the Northern hemisphere, and the suitable areas in the United States, China, and Russia accounted for 19.25%, 18.66%, and 13.15% of the total area worldwide, respectively. In China, the Inner Mongolia, Heilongjiang province, and Yunnan province occupied the largest proportions of the total area, namely 14.28%, 8.72%, and 6.18%, respectively. As revealed by ecological factors of each sampling site, S. baicalensis was resistant to low temperature but not to high temperature. The adaptive range of average annual precipitation is narrower than that of average annual air humidity. The suitable soils were mainly inceptisol, alfisol, and fluvisol. High temperature and rainy climate or excessively high soil bulk density was not conducive to the growth of S. baicalensis. The adoption of GMPGIS enabled to obtain areas with the greatest ecological similarity for S. baicalensis, which were reliable data supporting the exploration of resource distribution and reasonable introduction of S. baicalensis.
China ; Climate ; Plants, Medicinal ; Scutellaria baicalensis ; Soil

To screen and identify the endophytic fungal strains that could promote the accumulation of flavonoids in the callus of Scutellaria baicalensis. Seventeen endophytic fungal strains from S. baicalensis were used to prepare mycelium elicitors and fermentation broth elicitors. Their effects on flavonoid accumulation in S. baicalensis callus were then determined. The results showed that the fermentation broth elicitors of two strains(CL79, CL105) promoted the accumulation of flavonoids. The fermentation broth elicitor of CL79 significantly promoted accumulation of baicalin, wogonoside, baicalein, and wogonin, with the maximum levels increased by 37.8%, 40.4%, 44.7%, and 42.2%(vs. blank), respectively. Similarly, the fermentation broth elicitor of CL105 significantly promoted the accumulation of baicalin, wogonoside, baicalein, and wogonin, with the maximum levels increased by 78.1%, 140.9%, 275.6%, and 208.5%(vs. blank), respectively. CL79 was identified as Alternaria alternata, and CL105 as Fusarium solani. The fermentation broth elicitors of A. alternata CL79 and F. solani CL105 were able to promote the flavonoid accumulation in the callus of S. baicalensis, which enriched the resources of endophytic fungi and provided candidate strains for the development of microbial fertili-zers for improving the quality of S. baicalensis.
Scutellaria baicalensis ; Plant Roots ; Flavanones ; Flavonoids

Dihydroflavanol-4-reductase (Dfr) is a key enzyme that regulates the synthesis of anthocyanin and proanthocyanidin in the flavonoid biosynthesis pathway. To investigate the difference of dfr gene in Scutellaria baicalensis Georgi with different colors in the same ecological environment, three complete full-length sequences of dfr gene were cloned from the cDNA of S. baicalensis with white, purple-red and purple colors using homologous cloning and RACE techniques. The three genes were named Sbdfr1, Sbdfr2 and Sbdfr3, respectively, and their corresponding structures were analyzed. The results showed that all three Dfr proteins have highly conserved NADPH binding sites and substrate-specific binding sites. Phylogenetic analysis showed that they are closely related to that of the known S. viscidula (ACV49882.1). Analysis of key structural domains and 3D models revealed differences in the catalytically active regions on the surface of all three Dfr proteins, and their unique structural characteristics may provide favorable conditions for studying the substrate specificity of different Dfr proteins. qRT-PCR analysis shows that dfr was expressed at different level in all tissues except the roots of S. baicalensis in full-bloom. During floral development, the expression level of dfr in white and purple-flowered Scutellaria showed an overall upward trend. In purple-red-flowered Scutellaria, the expression first slowly increased, followed by a decrease, and then rapidly increased to the maximum. This research provides a theoretical basis for further exploring the mechanism and function of Dfr substrate selectivity, and are of great scientific value for elucidating the molecular mechanism of floral color variation in S. baicalensis.
Anthocyanins ; Cloning, Molecular ; Color ; Phylogeny ; Scutellaria baicalensis/genetics*

In the pharmacopoeia, many process parameters for the purification process of Scutellariae Radix are unclear. In this study, deterministic screening design combined with design space method was used to optimize the purification process of Scutellariae Radix extract. Nine method parameters such as mass fraction of solution(X_1), first acid precipitation pH(X_2) and first holding time(X_3) in the purification process were firstly studied by definitive screening design. The yield of baicalin was defined as the evaluation index. A stepwise regression method was used then to build quantitative models between evaluation index and method parameters and the three most critical impact parameters were determined. Probability-based design space was calculated and successfully verified with the experimental error simulation method. Finally, the second standing temperature, the first standing temperature and the pH value of the second acid precipitation were determined as the three most critical method parameters. The recommended operating space was as follows: the second standing temperature 5-7 ℃, the first standing temperature 13-15 ℃, and the pH of the second acid precipitation 1.5-1.7. Within this operating space, the baicalin yield in the purification process was over 80%, and the probability of reaching the standard was over 0.96. In this study, we optimized the effect of various parameters for the purification process of the Scutellariae Radix extract in the pharmacopoeia on the yield of baicalin and provided a reference for industrial production of the exact of Scutellariae Radix.
Drugs, Chinese Herbal ; Flavonoids ; Plant Extracts ; Scutellaria baicalensis

Scutellariae baicalensis is one of the most important traditional Chinese medicinal herbs, mainly distributed in Shandong and Hebei provinces. It has significant pharmacological effects such as antimicrobial activity, anti-inflammatory and antioxidation. Baicalin is one of its main effective components. However, baicalin's low bioavailability has restricted its clinical application. In recent decades, extensive studies have been carried out on the metabolism of baicalin at home and abroad. In order to provide scientific references for baicalin's further studies, this paper would not only review the advances in pharmacokinetics research of baicalin and Chinese herbal preparations containing baicalin, but also make a summary on research status of baicalin.
Drugs, Chinese Herbal ; pharmacokinetics ; Flavonoids ; pharmacokinetics ; Scutellaria baicalensis

Scutellariae Radix is one of the commonly used heat-clearing and damp-drying drugs in clinical practice. Establishment of the quality evaluation system for Scutellariae Radix is of great significance to ensure safety and effectiveness of clinical drug use.Scutellariae Radix pieces were prepared under different processing conditions with 3 softening methods: boiling,atmospheric steaming and pressurized steaming. High performance liquid chromatography( HPLC) method was used to determine the content of five flavonoids in Scutellariae Radix,and L*,a*,b*values representing color chromaticity of Scutellariae Radix powder were measured by colorimeter,then total color value E*was calculated. Simple correlation and canonical correlation analysis was used to explore the correlation between color of Scutellariae Radix powder and content of five flavonoids. The results showed that the contents of baicalin and wogonoside were significantly positively correlated with L*,b*and E*values,but negatively correlated with a*value. The contents of wogonin,apigenin,and melaleuca A were positively correlated with a*value,but negatively correlated with L*,b*,and E*values( P<0. 01). There was a significant negative correlation between the content of flavonoid glycosides and flavonoid aglycones( P<0. 01).All of these indicated that the color of Scutellariae Radix powder was significantly correlated with content of five flavonoids. The experiment results proved that when color difference between Huangqin pieces and medicinal materials was kept at ΔL*<6,Δb*<3,ΔE*<6,the total amount of the two glycosides in the pieces was about ±1. 5% of the medicinal materials; in this case,the total amount of the two glycosides was relatively high and stable,indicating that the color of Huangqin decoction pieces is a concrete manifestation of its intrinsic quality,and the chromaticity value detected by colorimeter can be used as a means to quickly evaluate the quality of Scutellariae Radix pieces. The results provide a new detection index for the characteristic quality evaluation system of Scutellariae Radix pieces.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; Flavonoids ; Scutellaria baicalensis

The aim of this study was to investigate the acute oral toxicity of fermented Scutellariae Radix (JKTMHGu-100) in rats and dogs. JKTM-HGu-100 was orally administered at a dose of 2,000 mg/kg in Sprague-Dawley rats. An escalating single-dose oral toxicity test in beagle dogs was performed at doses of 500, 1000, and 2000 mg/kg with 4-day intervals. Clinical signs, changes in body weight, mortality, and necropsy findings were examined for 2 weeks following oral administration. No toxicological changes related to the test substance nor mortality was observed after administration of a single oral dose of JKTM-HGu-100 in rats or dogs. Therefore, the approximate lethal dose (LD) for oral administration of JKTMHGu-100 in rats was considered to be over 2,000 mg/kg, and the maximum tolerance doses (MTDs) in rats and dogs were also estimated to be over 2,000 mg/kg. These results indicate that JKTM-HGu-100 shows no toxicity in rodents or non-rodents at doses of 2,000 mg/kg or less.
Administration, Oral ; Animals ; Body Weight ; Dogs ; Rats ; Rats, Sprague-Dawley ; Rodentia ; Scutellaria ; Scutellaria baicalensis ; Toxicity Tests

The aim of this study was to evaluate the anti-Helicobacter pylori activity of fractions and major aglycon compounds (baicalein, chrysin, oroxylin A, wogonin) of Scutellariae Radix. Minimum inhibitory concentration (MIC) measurement, DPPH radical-scavenging assay, DNA protection assay, and urease inhibition analysis were performed. The ethyl acetate (EtOAc) fraction showed the potent anti-Helicobacter activity, and therefore, compounds in the EtOAc fraction were subjected to further assay. The MICs of chrysin, oroxylin A, and wogonin against Helicobacter pylori 26695 were 6.25, 12.5 and 25 µg/mL, respectively. Baicalein exhibited the most effective DPPH radical-scavenging activity. DNA protection using Fenton reaction, chrysin, oroxylin A, and wogonin showed effective DNA protective effect. This result was also confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). Regarding Jack bean urease (0.5 mg/mL, 50 unit/mg) inhibition, 20 mM ofbaicalein and chrysin inhibited urease activity by 88.2% and 72.5%, respectively.
DNA ; Helicobacter pylori ; Microbial Sensitivity Tests ; Real-Time Polymerase Chain Reaction ; Scutellaria baicalensis* ; Scutellaria* ; Urease

BACKGROUND: Scutellaria baicalensis Georgi extract is used as a traditional herbal medicine. The efficacy of Scutellaria baicalensis Georgi extract is known for antioxidative activity, antiinflammation effect, antibacterial effect, inhibitory effect of melanin synthesis, sun protection effect, antiallergy effect, and etc. OBJECTIVE: We confirmed the cell viability or inhibitory effect of melanin synthesis in HaCaT (human keratinocyte cell line) and B16F10 (murine melanoma cell line) cells and the skin safety test through a clinical test (dermal irritation study) for Scutellaria baicalensis Georgi extract, according to the extraction methods. METHODS: We checked the cell viability, using MTT assay and inhibitory effect of melanin synthesis in B16F10 cells or HaCaT cells for thirty one Scutellaria baicalensis Georgi extract, according to the extraction methods. Then, we evaluated the skin safety for selected eight Scutellaria baicalensis Georgi extract through a primary dermal irritation test. RESULTS: Among the thirty one Scutellaria baicalensis Georgi extracts, according to the extraction methods, we selected eight Scutellaria baicalensis Georgi extracts that were not detected with cell toxicity in HaCaT cells and B16F10 cells, and could have inhibited the melanin synthesis in B16F10 cells. The selected eight Scutellaria baicalensis Georgi extracts identified the skin safety through a primary dermal irritation test. CONCLUSION: We expect clinical trials for whitening efficacy based on inhibitory effect of melanin synthesis and human skin safety for Scutellaria baicalensis Georgi extracts.
Cell Survival ; Herbal Medicine ; Humans ; Keratinocytes ; Melanins ; Melanoma ; Scutellaria ; Scutellaria baicalensis ; Skin ; Solar System

Oxidatively modified low density lipoprotein (LDL) could contribute to one of the atherosclerotic processes through its uptake by the scavenger receptor of macrophage. The aim of the present study was to examine whether ganghaungenin has an antioxidant effect. For the approach of the aim, a lipid peroxidation of LDL, the changes of degradation and negative charge of LDL, and LDL uptake in macrophage were measured after ganghaungenin was treated in the reaction process of LDL oxidation. The effective LDL oxidation was performed with treatment of 20 pM CuSO4 for 5 hours. Quercetin, one of the well-known antioxidant, was used as a positive control. The antioxdant effect of ganghaungenin on the LDL oxidation were examined at concentrations of both 40 p,M and 80 p,M for Sh. Ganghaungenin significantly inhibited the lipid peroxidation of LDL. It inhibited the oxidation-enhanced degradation and negative charge of LDL. Even 100 p,M of it did not have any toxic effects on macrophage. It inhibited the uptake of the oxidized LDL into macrophage. These data revealed that ganghaungenin obtained from Scutellaria Baicalensis Georgi was a potent antioxidant in inhibiting the oxidative modification of LDL. Conclusively, these findings indicate that ganghaungenin in physiologic concentrations could inhibit the oxidative modification of LDL in vivo, and suggest that ganghaungenin could be also used for the atherosclerosis prevention.
Antioxidants* ; Atherosclerosis* ; Lipid Peroxidation ; Lipoproteins ; Macrophages* ; Quercetin ; Receptors, Scavenger ; Scutellaria baicalensis