Optimization of Ultrasound-Assisted Extraction of Yields and Total Methoxyflavone Contents from Kaempferia parviflora Rhizomes.

The major bioactive components of Kaempferia parviflora (KP) rhizomes, 3,5,7,3',4'-pentamethoxyflavone (PMF), 5,7-dimethoxyflavone (DMF), and 5,7,4'-trimethoxyflavone (TMF), were chosen as the quantitative and qualitative markers for this plant material. In order to extract bioactive components (total methoxyflavones) from KP rhizomes, ultrasound-assisted extraction (UAE) was proposed as part of this study. Plackett-Burman design (PBD) and Box-Behnken design (BBD) were utilized to optimize the effects of UAE on extraction yields and total methoxyflavone contents in KP rhizomes. First, PBD was utilized to determine the effect of five independent variables on total yields and total methoxyflavone contents. The results indicated that the concentration of the extracting solvent (ethanol), the extraction time, and the ratio of solvent to solid were significant independent terms. Subsequently, BBD with three-level factorial experiments was used to optimize the crucial variables. It was discovered that the concentration of ethanol was the most influential variable on yields and total methoxyflavone contents. Optimum conditions for extraction yield were ethanol concentration (54.24% v/v), extraction time (25.25 min), and solvent-to-solid ratio (49.63 mL/g), while optimum conditions for total methoxyflavone content were ethanol concentration (95.00% v/v), extraction time (15.99 min), and solvent-to-solid ratio (50.00 mL/g). The relationship between the experimental and theoretical values was perfect, which proved that the regression models used were correct and that PBD and BBD were used to optimize the conditions in the UAE to obtain the highest yield and total methoxyflavone content in the KP rhizomes.

Bioactive Diterpenes from the Brazilian Native Plant (Moquiniastrum pulchrum) and Their Application in Weed Control.

Even today, weeds continue to be a considerable problem for agriculture. The application of synthetic herbicides produces serious environmental consequences, and crops suffer loss of their activity due to the appearance of new resistant weed biotypes. Our aim is to develop new effective natural herbicides that improve the problem of resistance and do not harm the environment. This work is focused on a bioassay-guided isolation and the characterization of natural products present in Moquiniastrum pulchrum leaves with phytotoxic activity and its preliminary application in weeds. Moquiniastrum pulchrum was selected for two reasons: it is an abundant species in the Cerrado region (the second most important ecosystem in Brazil, after the Amazon)-the explanation behind its being a dominant species is a major focus of interest-and it has traditional employment in folk medicine. Six major compounds were isolated in this plant: one flavone and five diterpenes, two of which are described for the first time in the literature. Four of the six compounds exhibited phytotoxic activity in the bioassays performed. The results confirmed the phytotoxic potential of this plant, which had not been investigated until now.

Hairy Roots of Scutellaria spp. (Lamiaceae) as Promising Producers of Antiviral Flavones.

We measured and studied the growth parameters and the qualitative and quantitative composition of the flavones of hairy roots of the Scutellaria genus: S. lateriflora, S. przewalskii and S. pycnoclada. Hairy roots were obtained using wild-type Agrobacterium rhizogenes A4 by co-cultivation of explants (cotyledons) in a suspension of Agrobacterium. The presence of the rol-genes was confirmed by PCR analysis. The hairy roots of the most studied plant from the Scutellaria genus, S. baicalensis, were obtained earlier and used as a reference sample. HPLC-MS showed the predominance of four main flavones (baicalin, baicalein, wogonin and wogonoside) in the methanol extracts of the studied hairy roots. In addition to the four main flavones, the other substances which are typical to the aerial part of plants were found in all the extracts: apigenin, apigetrin, scutellarin and chrysin-7-O-ß-d-glucuronide. According to the total content of flavones, the hairy roots of the studied skullcaps form the following series: S. przewalskii (33 mg/g dry weight) > S. baicalensis (17.04 mg/g dry weight) > S. pycnoclada (12.9 mg/g dry weight) > S. lateriflora (4.57 mg/g dry weight). Therefore, the most promising producer of anti-coronavirus flavones is S. przewalskii.

Metabolomics analysis of the soapberry (Sapindus mukorossi Gaertn.) pericarp during fruit development and ripening based on UHPLC-HRMS.

Soapberry (Sapindus mukorossi Gaertn.) is a multi-functional tree with widespread application in toiletries, biomedicine, biomass energy, and landscaping. The pericarp of soapberry can be used as a medicine or detergent. However, there is currently no systematic study on the chemical constituents of soapberry pericarp during fruit development and ripening, and the dynamic changes in these constituents still unclear. In this study, a non-targeted metabolomics approach using ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) was used to comprehensively profile the variations in metabolites in the soapberry pericarp at eight fruit growth stages. The metabolome coverage of UHPLC-HRMS on a HILIC column was higher than that of a C18 column. A total of 111 metabolites were putatively annotated. Principal component analysis and hierarchical clustering analysis of pericarp metabolic composition revealed clear metabolic shifts from early (S1-S2) to late (S3-S5) development stages to fruit ripening stages (S6-S8). Furthermore, pairwise comparison identified 57 differential metabolites that were involved in 18 KEGG pathways. Early fruit development stages (S1-S2) were characterized by high levels of key fatty acids, nucleotides, organic acids, and phosphorylated intermediates, whereas fruit ripening stages (S6-S8) were characterized by high contents of bioactive and valuable metabolites, such as troxipide, vorinostat, furamizole, alpha-tocopherol quinone, luteolin, and sucrose. S8 (fully developed and mature stage) was the most suitable stage for fruit harvesting to utilize the pericarp. To the best of our knowledge, this was the first metabolomics study of the soapberry pericarp during whole fruit growth. The results could offer valuable information for harvesting, processing, and application of soapberry pericarp, as well as highlight the metabolites that could mediate the biological activity or properties of this medicinal plant.

Bioassay-Guided Identification of the Antiproliferative Compounds of Cissus trifoliata and the Transcriptomic Effect of Resveratrol in Prostate Cancer Pc3 Cells.

The bioassay-guided fractionation of a CHCl3-MeOH extract from the stems of Cissus trifoliata identified an active fraction against PC3 prostate cancer cells. The treatment for 24 h showed an 80% reduction in cell viability (p ≤ 0.05) by a WST-1 assay at a concentration of 100 µg/mL. The HPLC-QTOF-MS analysis of the fraction showed the presence of coumaric and isoferulic acids, apigenin, kaempferol, chrysoeriol, naringenin, ursolic and betulinic acids, hexadecadienoic and octadecadienoic fatty acids, and the stilbene resveratrol. The exposure of PC3 cells to resveratrol (IC25 = 23 µg/mL) for 24 h induced significant changes in 847 genes (Z-score ≥ ±2). The functional classification tool of the DAVID v6.8 platform indicates that the underlying molecular mechanisms against the proliferation of PC3 cells were associated (p ≤ 0.05) with the process of differentiation and metabolism. These findings provide experimental evidence suggesting the potential of C. trifoliata as a promising natural source of anticancer compounds.

Flavones from Combretum quadrangulare Growing in Vietnam and Their Alpha-Glucosidase Inhibitory Activity.

Combretum quadrangulare Kurz is widely used in folk medicine in Eastern Asia and is associated with various ethnopharmacological properties including hepatoprotective, antipyretic, analgesic, antidysenteric, and anthelmintic activities. Previous phytochemical investigations reported the presence of numerous triterpenes (mostly cycloartanes, ursanes, lupanes, and oleananes) along with dozens of flavonoids. However, the extracts of C. quadrangulare and isolated flavonoids have not been evaluated for their alpha-glucosidase inhibition. In the frame of our efforts dedicated to the chemical investigation of Vietnamese medicinal plants and their biological activities, a phytochemical study of the MeOH extract of the leaves of C. quadrangulare using bioactive guided isolation was undertaken. In this paper, the isolation and structure elucidation of twelve known compounds, 5-hydroxy-3,7,4'-trimethoxyflavone (1), ayanin (2), kumatakenin (3), rhamnocitrin (4), ombuin (5), myricetin-3,7,3',5'-tetramethyl ether (6), gardenin D (7), luteolin (12), apigenin (13), mearnsetin (14), isoorientin (15), and vitexin (16) were reported. Bromination was applied to compounds 2 and 3 to provide four new synthetic analogues 8-11. All isolated and synthesized compounds were evaluated for alpha-glucosidase inhibition and antibacterial activity. Compounds 4 and 5 showed moderate antibacterial activity against methicillin-resistant Staphylococcus aureus while others were inactive. All compounds failed to reveal any activity toward extended spectrum beta-lactamase-producing Escherichia coli. Compounds 2, 4, 6-9, and 11-14 showed good alpha-glucosidase inhibition with IC50 values in the range of 30.5-282.0 µM. The kinetic of enzyme inhibition showed that 8 and 11 were noncompetitive type inhibition against alpha-glucosidase. In silico molecular docking model indicated that compounds 8 and 11 were potential inhibitors against enzyme α-glucosidase.

Sesquiterpenoids from Chrysanthemum indicum with Inhibitory Effects on NO Production.

Three new guaianolide lactones (1-3) and four new 9-oxonerolidol glucosides (5-8) together with 20 known compounds were isolated from the MeOH extract of the flowers of Chrysanthemum indicum. Their structures were elucidated based on the interpretation of NMR, HRESIMS, and electronic circular dichroism (ECD) data along with acid hydrolysis. Of the isolates, sesquiterpenoids 1-4 and 15 and flavones 17 and 18 exhibited inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide production in RAW 264.7 cells with IC50 values in the range 0.2-27.0 µM.

Anti-inflammatory Properties of Ethanolic Extract and 2″-O-ß-D-Glucopyranosyl-vitexin Obtained from Alternanthera tenella Colla Whole Plant.

Six flavonoids were identified and isolated from the ethanolic extract of Alternanthera tenella Colla (Amaranthaceae) whole plant (EEAT) including 2″-O-ß-D-glucopyranosyl-vitexin (A19). Flavonoids have anti-inflammatory activity; however, the 2″-O-ß-D-glucopyranosyl-vitexin anti-inflammatory property was not totally explored. The aim of the present study was to investigate the anti-inflammatory effects of ethanolic extract from A. tenella whole plant and isolated flavone C-glycoside A19 in models of inflammation. The oral administration (p.o.) of EEAT (30, 100, and 300 mg/kg), A19 (0.1, 1, and 10 mg/kg), and prednisolone (3 mg/kg) were tested against the carrageenan-induced paw edema in Swiss mice. The EEAT (100 mg/kg, p.o.), A19 (1 mg/kg, p.o.), and prednisolone (3 mg/kg, p.o.) were tested in the zymosan-articular inflammation, carrageenan-pleurisy, and complete Freund's adjuvant (CFA) models in Swiss mice. In silico analysis and search for structural relationships between vitexin derivatives flavones present in the EEAT and TNF-α inhibitors were performed. EEAT, A19, and prednisolone significantly inhibited (i) edema, mechanical hyperalgesia in carrageenan-induced paw inflammation; (ii) leukocyte migration and protein extravasation in carrageenan-induced pleurisy; (iii) knee edema, mechanical hyperalgesia, and leukocyte migration in articular inflammation induced by zymosan. Still the CFA induced the increase in myeloperoxidase and N-acetylglucosaminidase activities, EEAT, A19, and prednisolone significantly inhibited these enzymes. The in silico analysis showed that molecules with similar structure to apigenin and vitexin have a potential inhibition on the TNF system. This study confirms the anti-inflammatory properties of EEAT and A19. The C-glycosylated flavone A19 could be responsible for the EEAT anti-edematogenic and anti-hyperalgesic effects and a potential TNF-α inhibitor.

The phytochemistry and pharmacology of medicinal fungi of the genus Phellinus: a review.

Phellinus Quél is one of the largest genera of Hymenochaetaceae, which is comprised of about 220 species. Most Phellinus macro-fungi are perennial lignicolous mushrooms, which are widely distributed on Earth. Some Phellinus fungi are historically recorded as traditional medicines used to treat various diseases in eastern Asian countries, especially China, Japan and Korean. Previous phytochemical studies have revealed that Phellinus fungi produce diverse secondary metabolites, which mainly contain polysaccharides, flavones, coumarins, terpenes, steroids, and styrylpyranones. Pharmacological documents have demonstrated that Phellinus mushrooms and their compounds have a variety of bioactivities, such as anti-tumor, immunomodulation, anti-oxidative and anti-inflammation, anti-diabetes, neuro-protection, and anti-viral effects. This review surveys the literature reporting the isolation, characterization, and bioactivities of secondary metabolites from the fungi of the genus Phellinus, focusing on studies published in the literature up to April 2020. Herein, a total of more than 300 compounds from 13 Phellinus species and their isolation, characterization, chemistry, pharmacological activities, and relevant molecular mechanisms are comprehensively summarized.

[Structure Activity Relationship Study of Polymethoxylated Flavones Targeted Retinal Müller Cells for Prevention of Retinal Diseases].

Diabetic retinopathy (DR) is a retinal disease representing one of the main causes of vision loss in developed countries. In the early stage of DR, disruption of blood retinal barrier (BRB) is observed, and it will lead to vascular permeability and visual impairment. Therefore, protection against the breakdown of BRB may be useful strategy for prevention of DR. Matrix metalloproteinases (MMPs) plays an important role in the degradation of extracellular matrix proteins. In DR, they attribute to increased vascular permeability by degrading the junction proteins, such as occuldin and cadherin that are important to maintain the BRB junction complex. Müller cells constitute the main glial cells of the retina and are involved in many retinal functions. They are reported to be one of the MMP-producing cells in the retina. In this symposium review, I present the molecular mechanism of MMP expression in retinal Müller cells. In addition, I would like to introduce polymethoxylated flavones, nobiletin and the derivatives isolated from natural resource as novel MMP inhibitors, which may be applicable to prevention of DR.

Effect of methoxyflavones contained in Kaempferia parviflora on CRE-mediated transcription in PC12D cells.

The cAMP-response element (CRE) is critical in the formation of long-term memory. To prove the pharmacological effects of the methoxyflavones-rich residue (MRR) and its constituent methoxyflavones (1-9) extracted from the rhizomes of Kaempferia parviflora on the nervous system, we examined the effects of the MRR and methoxyflavones (1-9) on CRE-mediated transcription in PC12D cells. The MRR increased CRE-mediated transcription in PC12D cells. In addition, among methoxyflavones (1-9) isolated from MRR, compounds 1-4 increased CRE-mediated transcription. These results suggest that K. parviflora and methoxyflavone might be very useful materials for preventing and recovering from cognitive decline.

Detection of flavone C-glycosides in the extracts from the bark of Prunus avium L. and Prunus cerasus L.

The extracts from the bark of Prunus avium and Prunus cerasus have been analyzed by using high pressure liquid chromatography/electrospray ionization mass spectrometry. For the first time in the bark of Prunus species flavonoid C-glycosides have been detected. On the basis of the characteristic fragmentation patterns of their [M-H]- and [M + H]+ ions, three flavonoid C-glycosides have been identified, namely apigenin-6,8-di-C-glucoside (vicenin-2), apigenin-6-C-glucoside (isovitexin) and chrysin-8-C-glucoside. Taking into account the widely studied biological activities of flavonoid C-glycosides, the barks of these common fruit trees seem to be interesting materials of potential medical or cosmetic application.

Inhibitory Effect of Lygodium Root on the Cytochrome P450 3A Enzyme in vitro and in vivo.

PURPOSE: The aim of the present study was to investigate the interactions of the main components of Lygodium root (ie, p-coumaric acid, acacetin, apigenin, buddleoside and Diosmetin-7-O-ß-D-glucopyranoside) with cytochrome P450 3A enzyme activity both in vitro and in vivo. METHODS: In vitro inhibition of drugs was assessed by incubating rat liver microsomes (RLMs) with a typical P450 3A enzyme substrate, midazolam, to determine their 50% inhibitory concentration (IC50) values. For the in vivo study, healthy male Sprague Dawley rats were consecutively administered acacetin or apigenin for 7 days at the dosage of 5 mg/kg after being randomly divided into 3 groups: Group A (control group), Group B (acacetin group) and Group C (apigenin group). RESULTS: Among the five main components of Lygodium root, only acacetin and apigenin showed inhibitory effects on the cytochrome P450 3A enzyme in vitro. The IC50 values of acacetin and apigenin were 58.46 µM and 8.20 µM, respectively. Additionally, the in vivo analysis results revealed that acacetin and apigenin could systemically inhibit midazolam metabolism in rats. The Tmax, AUC(0-t) and Cmax of midazolam in group B and group C were significantly increased (P<0.05), accompanied by a significant decrease in Vz/F and CLz/F (P<0.05). CONCLUSION: Acacetin and apigenin could inhibit the activity of the cytochrome P450 3A enzyme in vitro and in vivo, indicating that herbal drug interactions might occur when taking Lygodium root and midazolam synchronously.

(3,3″)-Linked Biflavanones from Ouratea spectabilis and Their Effects on the Release of Proinflammatory Cytokines in THP-1 Cells.

Ouratea spectabilis is an arborous species traditionally used in Brazil as an anti-inflammatory agent. Four new (3,3″)-linked biflavanone O-methyl ethers, named ouratein A (1), B (2), C (3), and D (4), were isolated from the bark extract of the species. Ouratein A (1) is an enantiomer of neochamagesmine A, which has never been described before. The structures were elucidated by extensive spectroscopic data analyses, whereas their absolute configurations were defined by electronic circular dichroism data. Ouratein D (4) inhibited in vitro the release of the pro-inflammatory cytokine CCL2 by lipopolysaccharide-stimulated THP-1 cells (IC50 of 3.1 ± 1.1 µM), whereas TNF and IL-1ß release were not reduced by any of the biflavanones. These findings show ouratein D (4) as a selective CCL2 inhibitor, which may have potential for the development of new anti-inflammatory agents to prevent or treat cardiovascular diseases.

Oroxyloside ameliorates acetaminophen-induced hepatotoxicity by inhibiting JNK related apoptosis and necroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Oroxyloside is a natural flavonoid isolated from Scutellaria baicalensis Georgi (Lamiaceae) which is a Chinese herb widely used for liver diseases. However, its mechanisms on protecting against drug induced liver injury has not been investigated yet. AIM OF THE STUDY: To investigate the protecting effects and the primary mechanisms of oroxyloside on acetaminophen (APAP)-induced liver injury. MATERIALS AND METHODS: After a 12 h fasting period with free access to water, C57BL/6 mice were injected with APAP (300 mg/kg) intragastrically (i.g.) and 1 h later with oroxyloside (100 mg/kg, i.g.). When mice sacrificed, blood samples were collected from fundus venous plexus and liver tissues were collected. In addition, cells were incubated with 10 mM APAP alone and 10 mM APAP combined with 100 µM oroxyloside for 24 h. ELISA, TUNEL assay, qRT-PCR et al. were used to assess the effect of oroxyloside on ameliorating APAP-induced hepatotoxicity in vitro and in vivo. Western bolt and immunohistochemistry were used in the signaling pathway analysis. RESULTS: Oroxyloside administration significantly decreased the accumulations of CYP2E1, CYP1A2, IL-6, IL-1ß, ALT and AST induced by APAP in vivo. In addition, oroxyloside inhibited the APAP-induced JNK related apoptosis by enhancing the antioxidant defenses, reversing ER-stress and keeping the mito-balance of liver cells in vivo and in vitro. Furthermore, oroxyloside protected the liver cells from necroptosis by affecting JNK pathway. CONCLUSION: Oroxyloside acted as a protective agent against APAP-induced liver injury through inhibiting JNK-related apoptosis and necroptosis.

Flavones Contents in Extracts from Oroxylum indicum Seeds and Plant Tissue Cultures.

Oroxylum indicum (L.) Benth. ex Kurz or Pheka, is a plant in the Bignoniaceae family with various traditional uses. The mature fruits promote anti-helminthic and stomachic effects, while the seeds have been used as a purgative and for the relief of tonsil pain. The young fruits are popularly consumed as vegetables, while the seeds are one of the components in traditional drink formulations. To develop new plant raw material sources, a plant tissue culture technique was used to generate plant tissue cultured samples from the seeds of O. indicum. Plant tissue cultured samples were collected from three different growth stages; 4 days, then at 3 and 9 weeks, and prepared as crude extracts by maceration with ethanol, along with the seed raw material sample. A high performance liquid chromatographic (HPLC) method was used for quantitative analysis of the contents of the three major flavones; baicalin, baicalein, and chrysin in the extracts from the seeds and plant tissue cultured samples of this plant. Baicalin was found in the highest amount among these three flavones in all extracts. The seed extract contained the highest baicalin content (24.24% w/w in the extract), followed by the shoot extract from tissue-cultured plant at week 3 (14.78% w/w of the extract). The amounts of chrysin in all O. indicum showed the same trend as the contents of baicalin, but the amounts were lower, while baicalein was accumulated at the lowest amount among three flavonoids and the amounts were quite stable in all O. indicum extracts. From the results, O. indicum seed and plant tissue cultured extracts have potential as sources of flavones, which could be further developed as health products in the future.

Anti-glycating and anti-oxidant compounds from traditionally used anti-diabetic plant Geigeria alata(DC) Oliv. & Hiern.

A new sesquiterpene lactone geigerianoloide (1) and four known flavonoids axillarin (2), quercetin (3), 3-methoxy-5,7,3',4'-tetrahydroxy-flavone (4) and hispidulin (5) were isolated from Geigeria alata (DC) Oliv. & Hiern. (Asteraceae). Structures were deduced using 1H- and 13C- NMR spectroscopy, mass spectrometry, while the structure of compound 1 was also deduced using X-ray crystallography technique.Geigeria alata is traditionally used for diabetes, therefore compounds were tested for anti-glycation activity, in which compounds 2 and 3 showed potent activities (IC50 values of 246.97 ± 0.83 and 262.37 ± 0.22 µM, respectively) compared to IC50 value 294.50 ± 1.5 µM of rutin. Moreover, compound 4 exhibited a comparable activity to rutin (IC50 = 293.28 ± 1.34 µM). Compound 5 showed a weak activity.Compounds 2, 3, and 4 exhibited potent DPPH radical scavenging activity (IC50 = 0.1 ± 0.00, 0.13 ± 0.00 and 0.15 ± 0.01 µM, respectively). Compounds 2, 3, and 4 demonstrated significant superoxide anion scavenging activity with IC50 values of 0.14 ± 0.001, 0.17 ± 0.00, and 0.11 ± 0.006 µM, respectively.

Anti-inflammatory activity of 4',6,7-trihydroxy-5-methoxyflavone from Fridericia chica (Bonpl.) L.G.Lohmann.

Fridericia chica, Bignoniaceae, is a tropical tree-creeper used as a traditional remedy for a number of diseases, highlighting inflammation. Our objective was to corroborate the popular anti-inflammatory use of the hydroethanolic extract from the leaves (HEFc) and of its isolated 4',6,7-trihydroxy-5-methoxyflavone (5-O-methylscutellarein) [1], described here for the first time. Quantitative analysis indicated 8.77 ± 0.23 mg/g of this compound in the extract. Neither HEFc nor [1] was cytotoxic in vitro. In LPS-induced peritonitis in mice, oral pre-treatment with HEFc or [1] led to decreased leukocyte migration to the peritoneal cavity and a reduction in the concentrations of pro-inflammatory cytokines (TNFα and IL-1ß). Also, the anti-inflammatory cytokine IL-10 was enhanced following treatment with [1]. Overall, these results validate the traditional use of Fridericia chica as anti-inflammatory, and indicate that the compound 5-O-methylscutellarein may participate in this effect.

Total flavones of Rhododendron simsii Planch flower protect rat hippocampal neuron from hypoxia-reoxygenation injury via activation of BKCa channel.

OBJECTIVES: To study the effects of total flavones of Rhododendra simsii Planch flower (TFR) on hypoxia/reoxygenation (H/R) injury in rat hippocampal neurons and its underlying mechanism. METHOD: Model of H/R was established in newborn rat primary cultured hippocampal neuron. Lactate dehydrogenase (LDH) and neuron-specific enolase (NSE) activity as well as malondialdehyde (MDA) content in cultured supernatants of the neurons were examined. Methyl thiazolyl tetrazolium assay and Hoechst33258 staining were, respectively, used to detect cell viability and apoptosis of neurons. Protein expression and current of BKCa channel were assessed by using Western blotting and whole-cell patch-clamp methods, respectively. KEY FINDINGS: In the ranges of 3.7-300 mg/l, TFR significantly inhibited H/R-induced decrease of neuronal viability and increases of LDH, NSE and MDA in the supernatants as well as apoptosis; TFR 33.3, 100 and 300 mg/l markedly increased current of BKCa channel rather than the BKCa channel protein expression in the neurons. CONCLUSIONS: Total flavones of R. simsii Planch flower had a protective effect against H/R injury in rat hippocampal neuron, and activation of BKCa channel may contribute to the neuroprotection.

A review of the ethnopharmacology, phytochemistry, pharmacology, and quality control of Scutellaria barbata D. Don.

ETHNOPHARMACOLOGICAL RELEVANCE: Scutellaria barbata D. Don (S. barbata) is a well-known perennial herb that is used in traditional Chinese and Korean medicine. In China, it is known as Ban Zhi Lian, while in Korea, it is known as Banjiryun. In the Traditional Chinese Medicine (TCM) system, S. barbata has heat-clearing and detoxifying properties (Qingre Jiedu in Chinese). AIM OF THE REVIEW: To provide a systematic review on current multifaceted understanding of S. barbata, with particular emphasis on the correlation between its traditional applications and pharmacological activities. MATERIALS AND METHODS: All available S. barbata-related information from internet databases, including PubMed, Science Direct, Elsevier, China National Knowledge Internet, and Google Scholar (up to October 2018) were searched. Additional information was gathered from classical books on Chinese Herbals, Chinese Pharmacopoeia, and so on. RESULTS: In the TCM system, S. barbata is mainly prescribed for its heat-clearing and detoxifying effects. More than 203 compounds have been isolated and identified from this herb, with neo-clerodane diterpenoids and flavonoids as the main compounds. Most neo-clerodanes have been demonstrated to have cytotoxic effects against different cancer cell types in vitro. The S. barbata extracts exhibited anti-inflammatory, anti-microbial, antitumor, and other pharmacological activities. To add, flavonoids, including wogonin, baicalein, apigenin, naringenin, and scutellarin, were identified as the key to quality control. CONCLUSIONS: The heat-clearing effects of S. barbata could be attributed to its anti-inflammatory and hepatoprotective activities, whereas its detoxifying effects might be due to the anti-microbial functions of neo-clerodane diterpenoids and flavones. S. barbata may display anti-tumor effects and through active ingredient analysis, neo-clerodane diterpenoids are suggested to be its representative compounds. Overall, many pre-clinical studies have been conducted but very little concrete evidences are available on its specific effects, which are of therapeutic relevance.