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Hyperuricemia is a clinical condition characterized by an elevated level of serum uric acid and is a key risk factor for the development of gout and metabolic disorders. The existing urate-lowering therapies are often impractical for certain patient populations, providing a rationale to explore new agents with improved safety and efficacy. Here, we discovered that Salvia plebeia extract inhibited the enzyme activity of xanthine oxidase, which is a key enzyme generating uric acid in the liver. In an animal model of hyperuricemia, S. plebeia extract reduced serum urate to the levels observed in control animals. The urate-lowering effect of S. plebeia extract in vivo was supported by the identification of compounds that inhibit xanthine oxidase enzyme activity in vitro. Nepetin, scutellarein, and luteolin contributed significantly to S. plebeia bioactivity in vitro. These compounds showed the highest potency against xanthine oxidase with IC50 values of 2.35, 1.74, and 1.90 µM, respectively, and were present at moderate quantities. These observations serve as a basis for further elaboration of the S. plebeia extracts for the development of new therapeutics for hyperuricemia and related diseases.

Plebein A ( 1 ), a sesquiterpenoid with a novel skeleton and another sesquiterpenoid, plebein B ( 2 ), and four new diterpenoids plebeins C-F ( 4–7 ), along with six known compounds were isolated from the whole plant of Salvia plebeia R. Br. The absolute configuration of 2 was established by an X-ray crystallographic study. In addition, compounds 4 , 6 and 9 showed anti-proliferative activity against CaCo2 and MCF-7 cell lines, with IC 50 values ranging from 9.65 μM to 45.96 μM.

In traditional Korean/Asian medicine, Salvia plebeia R.Br. (S. plebeia) leaves are used to treat inflammatory diseases, including dermatitis, cough, asthma and toothache. Recently, S. plebeia leaves have been applied in skin care, as they promote skin lightening and elasticity. Therefore, the present study investigated the anti-aging effects of S. plebeia leaf methanolic extract and its fractions (dichloromethane, ethylacetate and n-butanol). The results of a whole-cell patch clamp analysis indicated that the methanolic extract mediated ultraviolet (UV)-induced photoaging-associated ion channels, transient receptor potential vanilloid 1 (TRPV1) and calcium release-activated calcium channel protein 1 (ORAI1) channel activity in HEK293T cells overexpressing TRPV1 or ORAI1 and STIM1. Electrophysiological analysis revealed that the butanol fraction inhibited capsaicin-induced TRPV1 (84±8% at -60 mV/86±1% at 100 mV at 100 µg/ml) and ORAI1 (87±2% at -120 mV at 100 µg/ml) currents. Furthermore, the dichloromethane and hexane fractions inhibited tyrosinase activity by 32.4±0.69 and 22.6±0.96% at 330 µg/ml, respectively. Furthermore, the ethylacetate and butanol fractions inhibited elastase activity by 65.2±1.30 and 31.7±1.23% at 330 µg/ml, respectively. Tyrosinase and elastase, which are UV-induced photoaging-associated enzymes, regulate skin pigmentation and wrinkle formation, respectively. The results of the present study indicated that S. plebeia leaves may be a novel treatment for UV-induced photoaging.

Salvia plebeia R.Br. (SPRB) is a natural resource that exhibits various biological activities. However, its effects on inflammatory diseases are not yet well characterized. This study aimed to evaluate the inhibitory effects of a compound derived from SPRB on interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) activation. The chemical structure of active compounds isolated from the EtOAc-soluble fraction of SPRB were elucidated by comparison with spectroscopic nuclear magnetic resonance (NMR) and electrospray ionization mass spectrometry (ESI–MS) data in the literature, which resulted in the identification of 22 known compounds. All of the isolated compounds were evaluated for potentially higher inhibitory effects on IL-6-induced STAT3 activation in Hep3B cells using a luciferase reporter assay. Furthermore, the protein levels of p-STAT3, p-ERK, and p-JAK2 in IL-6 induced U266 cells were regulated in the presence of cirsimaritin from SPRB by western blot assay. Based on these findings, we suggest that SPRB has the potential to inhibit IL-6-induced STAT3 activation and should be considered in functional food and pharmaceutical applications.

Salpleflavone, a new flavone glucoside bearing a sinapinoyl moiety, was isolated from the aerial parts of Salvia plebeia R. Br., together with three known compounds, salplebeone A, salplebeone D and 6- O-methyl-scutellarein. The structure of the new compound was established by detailed analyses of the spectroscopic data, especially 1D and 2D NMR and HR-ESI-MS.

Salvia plebeia R. Br. is a traditional Chinese medicinal herb that has been widely used for the treatment of many inflammatory diseases such as hepatitis. However, the underlying molecular mechanism about the hepatoprotective effects of S. plebeia remains largely unknown. Here, we investigated the antioxidant activities and anti-inflammatory effects of ethanol extracts of S. plebeia (SPEE) in the zebrafish model. Firstly, we determined the chemical compositions of SPEE and identified three major constituents by using GC-MS analysis. After that, SPEE exhibited significantly antioxidant properties in the LPS-induced zebrafish embryos, and the enzyme activities of ROS, CAT and SOD were obviously inhibited in a dose-dependent manner. Secondly, SPEE greatly reduced fat vacuoles (HE staining), lipid accumulation (Oil O staining) and hepatocyte fibrosis (Gemori staining) in the thioacetamide (TAA)-induced hepatocyte injury of adult zebrafish. Meanwhile, the NO contents and lipid metabolism-related genes were substantially down-regulated after SPEE exposure. Thirdly, we used RNA-Seq analysis to identify the differentially expressed genes (DEGs) after SPEE exposure in adult zebrafish liver. The results showed that 1289 DEGs including 558 up-regulated and 731 down-regulated were identified between the TAA + SPEE and TAA groups. KEGG pathway and GO functional analysis revealed that steroid biosynthesis, oxidation-reduction and innate immunity were significantly enriched. Mechanistically, SPEE can considerably reduce the cell apoptosis of hepatocytes and promote the translocation of Nrf2 protein from the nucleus to the cytoplasm in TAA-induced zebrafish. Moreover, SPEE can modulate various inflammatory cytokines and immune genes both in the control and H2O2-stimulated conditions. The pro-inflammatory cytokines such as IL-1β and TNF-α was markedly up-regulated but the anti-inflammatory cytokines such as TGF-β was greatly down-regulated after SPEE treatment. In addition, some key genes in the TLR signaling were also activated in the H2O2-stimulated conditions. In summary, our results suggested that SPEE had an important role in the antioxidant and anti-inflammatory effects in zebrafish in the near future. Some of the components identified in this study may be served as potential sources of new hepatoprotective compounds for the treatment of inflammatory diseases.

This study was designed to investigate the antiobesity effects of Salvia plebeia R. Br. ethanolic extracts (SPE) in mice fed high-fat diets (HFD). Male C57BL/6J mice were randomly assigned to four groups: normal diet (Chow), high-fat diet (HFD, 45% fat), HFD+SPE 200 (200 mg/kg b.w.), and HFD+SPE 400 (400 mg/kg b.w.). Extracts were administered orally every day for 8 weeks. Increases in body/fat weight and feed efficiency ratio were monitored in all mice. In addition, obesity resulting from feeding HFD to the mice was confirmed by the increase of glucose level, aspartate transaminase, alanine transaminase, triglyceride (TG), high-density lipoprotein cholesterol, very low-density lipoprotein-c, leptin, and adiponectin in blood. The SPE-treated mice gained less body and mesenteric/subcutaneous adipose tissues weights and had lower TG, very low-density lipoprotein cholesterol, leptin, and glucose level in serum, compared to the HFD group. Moreover, histopathological examinations revealed that the size of adipocytes in liver and adipose tissue was significantly decreased by SPE, compared to the HFD group. The expression of adipogenesis transcription factors (e.g., peroxisome proliferator activated receptor γ and CCAAT/enhancer binding protein α) and lipogenesis-related target genes (adipocyte fatty acid-binding protein 2, lipoprotein lipase, fatty acid synthase, and sterol regulatory element-binding transcription factor 1c) in HFD-induced obese mice was decreased by SPE treatment. These results suggest that SPE attenuates the fat accumulation in HFD-induced obese mice by suppressing the expressions of genes related to adipogenesis and lipogenesis activity. Therefore, SPE could be developed as a potential therapy for reduction of body weight and antiobesity intervention.

The interleukin-6 (IL-6) family of cytokines plays a key role in the pathogenesis of rheumatoid arthritis and osteoporosis through the regulation of bone formation and resorption. In this study, it was observed that ethanol extract of Salvia plebeia R.Br. (S.P-EE) inhibited IL-6-induced signaling cascade including phosphorylation of JAK2/STAT3 and ERK. Subsequently, it was examined whether S.P-EE treatment could recover bone loss in ovariectomized (OVX) mice. Indeed, S.P-EE exhibited both preventive and therapeutic effect on OVX-induced bone loss in trabecular microarchitecture along with significant increase in bone mineral density and content. To understand the mechanism of action of S.P-EE in bone metabolism, the effect of S.P-EE on osteoclast differentiation and activity was investigated. S.P-EE significantly inhibited RANKL-induced osteoclast differentiation by suppressing phosphorylation of MAPK and Akt, and expression of NFATc1 and osteoclast marker genes. S.P-EE also inhibited bone-resorbing activity of osteoclasts. Furthermore, isolation and identification of the active compounds which are responsible for the inhibitory effect of S.P-EE on osteoclast differentiation was carried out. Six major flavonoids and plebeiolide A-C were isolated and examined their effects on osteoclast differentiation. Luteolin and hispidulin, and plebeiolide A and C, not B exhibited potent inhibitory activity on RANKL-induced osteoclast formation.

Patient: Female, 54 Final Diagnosis: Salvia intoxication Symptoms: Frequent nausea Medication: Thyroxine Clinical Procedure: — Specialty: Hematology Objective: Unusual clinical course Background: Previous reports suggest that homoplantaginin, one of the compounds isolated from Salvia plebeia, has a protective and therapeutic effect on hepatocyte injury. We present a case of serious liver and kidney damage due to incorrect use of Salvia plebeia in a patient with a history of thyroid tumorectomy, who was successfully treated for poisoning with blood purification and systemic, comprehensive critical care. Case Report: A 54-year-old female patient with salvia intoxication combined with multiple organ dysfunction was transported to our emergency center by ambulance after presenting with nausea, vomiting, and skin yellowing. On arrival, she exhibited fatigue, dizziness, lightheadedness, yellowish discoloration of her skin, breathing difficulties, and low back pain, all of which was suggestive of salvia intoxication combined with multiple organ dysfunction. The treatment strategy was to immediately speed up the excretion of toxins and administered blood purification therapy. She also displayed disseminated intravascular coagulation (DIC), which was successfully treated with plasma infusion of blood coagulation factor combined with LMWH acupuncture therapy. Conclusions: Salvia plebeia should only be considered for use in patients who have infectious disease or oxidative stress related disease and only at an appropriate dose. In addition, for patients with salvia poisoning, prompt administration of blood purification therapy and systemic comprehensive measures involving multiple supportive therapies can save such patients.

Salvia plebeia R. Br. (SP), has been widely used in traditional Chinese medicine (TCM). It contains a number of chemical components and reported to possess a variety of pharmacological activities. SP is distributed in many countries such as China, Korea, Japan, Afghanistan and India. SP was first described in Compendium of Materia Medica in the Ming dynasty. The aim of this review is to compile all the information reported in the literature on SP. This review covers traditional uses, including 16 TCM classics and 21 traditional prescriptions; a total of 93 compounds from SP have been reported, including flavonoids, monoterpenoids, sesquiterpenoids, diterpenoids, triterpenes, phenolic acids etc; biological actives such as antioxidant, antimicrobial, hypoglycaemic, anti-inflammatory, analgesic, sedative, antiasthmatic, antiviral, antitumour, hepatoprotective effects etc. In addition, this paper also compiled the quality control studies and clinical applications. The future prospects and the existing problems of SP were also discussed. Overall, we believe this review will be a comprehensive record of SP for researchers to refer for carrying out for further research.

Background and aims Salvia is the largest genus within Lamiaceae, with about 980 species currently recognized. East Asia, with approx. 100 species, is one of the three major biodiversity centres of Salvia. However, relationships within this lineage remain unclear, and the staminal lever mechanism, which may represent a key innovation within the genus, has been understudied. By using six genetic markers and nearly comprehensive taxon sampling, this study attempts to elucidate relationships and examine evolutionary trends of staminal development within the East Asia (EA) Salvia clade. Methods Ninety-one taxa of EA Salvia were sampled and 34 taxa representing all other major lineages of Salvia were included for analysis. Two nuclear [internal transcribed spacer (ITS) and external transcribed spacer (ETS)] and four chloroplast (psbA-trnH, ycf1-rps15, trnL-trnF and rbcL) DNA markers were used for phylogenetic analysis employing maximum parsimony (MP), maximum likelihood (ML) and BEAST, with the latter also used to estimate divergence times. Key results All Salvia species native to East Asia form a clade, and eight major subclades (A-G) were recognized. Subclade A, comprising two limestone endemics (S. sonchifolia and S. petrophila), is sister to the remainder of EA Salvia. Six distinct stamen types were observed within the EA clade. Stamen type A, with two fully fertile posterior thecae, only occurs in S. sonchifolia and may represent the ancestral stamen type within EA Salvia. Divergence time estimates showed that the crown of EA Salvia began to diversify approx. 17.4 million years ago. Conclusions This study supports the adoption of a broadly defined Salvia and treats EA Salvia as a subgenus, Glutinaria, recognizing eight sections within this subgenus. Stamen type A is ostensibly plesiomorphic within EA Salvia, and the other five types may have been derived from it. Staminal morphology has evolved in parallel within the EA Salvia, and staminal structure alone is inadequate to delimit infrageneric categories.

A new skeleton of diterpenoid, 1,2,3,4,4α,9,10,10α-octahydro-(4α-hydroxyymethyl) -1,1-dimethyl-9-(1-methylethyl)-(2S,3S,4αR,9R,10αS)-2,3,5,7-phenanthrenetertrol, named plebeianiol A (1), along with four known diterpenoids (2-5), were isolated from Salvia plebeia R. Br. Their structures were determined on the basis of spectral analysis. In the bioactivity tests, compounds 1, 2 and 5 showed 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities with IC50 values of 20.0-29.6 µM. In addition, these three compounds had significant inhibitory effects on reactive oxygen species (ROS) production in lipopolysaccharide (LPS)-induced macrophages. Compounds 1-3 inhibited nitric oxide (NO) production in LPS-induced macrophages with IC50 values of 18.0-23.6 µM. These results showed that compounds 1, 2 had significant antioxidant and anti-inflammatory activities and might provide basis for the treatment of diseases associated with oxidative lesions and inflammation.

*YD Life Science Research Institutes, YD Life Science Co. Ltd., Seongnam 462-807, Korea.**Department of Food and Nutrition, Kongju National University, Yesan 340-802, Korea.ABSTRACT : This study was carried out to investigate the effects of Salvia plebeia R. Br. ethanolic extract with differentaspects (stem/leaf and whole plant) on differentiation and lipid accumulation in 3T3-L1 preadipocytes. The morphologicalchanges and the degrees of lipid accumulation in 3T3-L1 cells were measured by Oil Red O staining and intra-cellular trig-lyceride (TG) assay. The mRNA expressions of special peroxisome proliferation activated receptor- genes (PPAR), CCAAT/enhancer-binding protein (C/EBPα), fatty acid synthase (FAS) and lipoprotein lipase (LPL) were detected by reverse tran-scriptase polymerase chain reaction (RT-PCR). The 50% ethanolic extracts (100μg/mL) of stem and leaf (SALE) and 30%ethanolic extracts (100 g/mL) of whole plant (SAE) from Salvia plebeia R. Br. were significantly attenuated lipid accumula-tion during adipogenesis in 3T3-L1 cells. Ethyl acetate-soluble fractions (50μg/mL) significantly inhibited lipid dropletaccumulation in 3T3-L1 cells. In addition, SALE induced down-regulation of specific adipogenic transcriptional factors (C/EBPα and PPARγ) and target genes (FAS and LPL) during adipogenesis. Salvia plebeia R. Br. may be used as a safe and effi-cient natural substance to manage obesity.Key Words : Salvia plebeia, 3T3-L1, Adipogenesis, C/EBP α, PPARγ, FAS, LPL

This study was conducted to investigate the effects of water extract from Rosa multiflora and Rosa multiflora complex on lipid metabolism in rats fed a high cholesterol diet. Experimental rats were divided into four groups, which were composed of normal diet group (N group), high cholesterol diet group (HF group), high cholesterol and 5% Rosa multiflora diet group (HR group), and high cholesterol and Rosa multiflora complex diet group (HRC group). Rosa multiflora complex is composed of Duchesnea chrysantha, Salvia plebeia R. BR., and Sasa borealis. The serum triglyceride (TG) content of the HF group was significantly higher than that of the N group, whereas that of the HRC group was significantly lower. Serum high-density lipoprotein-cholesterol contents of the HR and HRC groups were significantly higher than that of the HF group. The serum total cholesterol and low-density lipoprotein-cholesterol contents of the HF group were significantly higher than those of the N group, and especially the atherogenic index of the HRC group was significantly reduced compared to the HF group. The liver TG and total cholesterol contents of the HF group were significantly increased compared to the normal diet group, while those of the HR and HRC groups were significantly decreased compared to the HF group. Fecal total lipid and total cholesterol contents of the HR and HRC groups were significantly increased compared to the HF group. Uridine 5'-diphospho (UDP)-glucuronyl transferase activity of the HR and HRC groups were increased compared to the HF group. Total bile acid contents of the HR and HRC groups were increased compared to the HF group, and that of the HRC group was significantly increased compared to the HF groups. These results suggest that Rosa multiflora supplementation has powerful health benefits due to UDP-glucuronyl transferase activity, bile acid, and lipid metabolism.

The substitute tea was manufactured from the leaves of Salvia plebeia R. Br. (SPR) that have anti-inflammatory and antioxidative activities. Total polyphenols and flavonoids in SPR were 71.8±4.74 GAE mg/g and 38.7±2.95 QUE mg/g, respectively. DPPH radical scavenging activity of SPR water extract had an RC50 of 16.9 μg/mL. SPR inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) production with an IC50 of > 100 μg/mL. Medium and large leaves were used in the SPR substitute tea (SPRT). The water content was dissipated on roasting within approximately 10 minutes, and the tea obtained from fan-firing for a total 120 minutes was evaluated as most superior. Flavor was positively correlated with the taste and general preference. SPRT maintained its anti-oxidative activity without significant changes on roasting or fan-firing even after the heat treatment. The appropriate weight of a tea bag for one serving was 1.0 g. The study results indicated that SPR is a potential resource for the development of food or ingredients with anti-inflammatory properties.

Two new flavones neocafhispidulin (1) and 6″-O-acetyl homoplantaginin (2), together with 10 known flavones and 1 polyphenol were isolated from the whole plants of Salvia plebeia. R. Br. Compounds 3 and 4 were reported from this plant for the first time. Their structures were determined by spectral analyses. Compounds 1-13 were evaluated for their anti-tyrosinase and anti-inflammatory activities. The results showed that compounds 1, 5, 8, 10 and 11 exhibited anti-tyrosinase activities, and compounds 3, 4 and 13 showed potential anti-inflammatory activities.

This study examined changes in antioxidant activity as well as contents of rosmarinic acid, homoplantaginin, and luteolin, which is the main substance of Salvia plebeia R. Br. (SPR) known to have anti-inflammatory efficacy, according to drying, blanching, and fermentation conditions. Rosmarinic acid content was 16.42 ㎎/g upon hot-air drying and 10.19 ㎎/g upon hot-air drying after blanching, and there was no significant difference in the case of leaf and root freezing or cold-air drying. Rosmarinic acid content was 8.69 and 8.15 ㎎/g in the case of air-drying in the shade and freeze-drying, respectively, and decreased to 0.05 ㎎/g or undetected after fermentation. SPR processed by freeze-drying, cold-air drying in the shade, and hot-air drying showed ABTS radical scavenging ability over 98.5% at a concentration over 500 μg/mL as well as excellent radical scavenging ability of 87.3% in the case of hot-air drying after blanching. Root showed lower ABTS radical scavenging ability than leaves. SOD-like activity was measured to be 6.1～27.8% at a concentration of 1,000 ㎍/mL, which was significantly difference from ABTS radical scavenging ability. As rosmarinic acid and homoplantagine, an anti-inflammatory material contained in SPR, are almost undetectable after oxidation fermentation during processing, hot-air drying after blanching or drying seems to be suitable to develop SPR as a functional substance.

The effect of light intensity on content of total polyphenol and activities of antioxidizing enzymes of P. frutescens var. acuta Kudo (Perilla) and S. plebeia R. Br. (Salvia) under a controlled environment was investigated. The three treatments used were T1, 300 μmol·m-2·s-1 PPFD for 38 days; T2, 300 μmol·m-2·s-1 PPFD for 31 days and 500 μmol·m-2·s-1 PPFD for additional 7 days; and T3, 500 μmol·m-2·s-1 PPFD for 38 days. After 38 days of cultivation, shoot and root growth, contents of total chlorophyll, anthocyanin and total polyphenol, and activities of antioxidizing enzymes were measured. The shoot and root growth decreased in the T2 and T3 treatments. Moreover, the incidence of tip burn increased in the T3 treatment in both species. Anthocyanin content in the Perilla decreased, while total chlorophyll content of the Salvia increased, in the T2 and T3 treatments as compared to the T1 treatment. Total polyphenol content and activities of antioxidizing enzymes increased in the Perilla in the T3 and in the Salvia in the T2 treatments.

Nine new sesquiterpenoid lactones and 11 known analogues were isolated from the aerial parts of Salvia plebeia R.Br. Their structures were elucidated via HRESIMS and NMR data, and their absolute configurations were defined via electronic circular dichroism data, X-ray crystallographic analysis, and the modified Mosher’s ester method. Compounds 1–20 were investigated for their ability to inhibit LPS-stimulated nitric oxide production in murine macrophage cells. Of the isolates, epi-eudebeiolide C (20) showed the highest inhibitory effect (IC50 of 17.9 μM). mRNA and protein expression of inducible nitric oxide synthase (iNOS), but not that of cyclooxygenase-2 (COX-2), was dose-dependently decreased by 20 in LPS-activated RAW 264.7 cells. Based on a mechanistic study involving the nuclear factor-κB (NF-κB) signaling pathway, the anti-inflammatory effect of 20 was attributed to NF-κB activation blockade via inhibition of NF-κB (IκB) phosphorylation. Therefore, 20 might be a potential candidate for relieving i...

This study investigated the chemical composition changes of Salvia plebeia R.Br. cultivated under different light sources, including florescent light and sunlight. The plants were exposed to fluorescent light for four months and sunlight and then examined for the next 5–7 months. Plants were harvested monthly during the seven months, and we examined whether the difference in light source affected the phenolic and flavonoid contents and antioxidant activity. A simple and reliable HPLC method using a PAH C18 column was applied for the quantitative analysis of two triterpenoids from the S. plebeia groups. Oleanolic acid (OA) and ursolic acid (UA) showed good linearity (R2 > 0.9999) within the test ranges (0.005–0.05 mg/mL), and the average percentage recoveries of the OA and UA were 95.1–104.8% and 97.2–107.1%, respectively. The intra- and inter-day relative standard deviations (RSDs) were less than 2.0%. After exposure to sunlight, the phenolic contents, including rosmarinic acid, showed a reduced tendency, whereas the flavonoid contents, including homoplantaginin and luteolin 7-glucoside, were increased. The content of the triterpenoids also showed an increased tendency under sunlight irradiation, but the variance was not larger than those of the phenolic and flavonoid contents. Among experimental groups, the group harvested at six months, having been exposed to sunlight for two months, showed the most potent antioxidant activity. Therefore, these results showed that the chemical composition and antioxidant activities of S. plebeia R.Br. was affected from environmental culture conditions, such as light source. Our studies will be useful for the development of functional materials using S. plebeia R.Br.

To determine the compounds responsible for its anti-influenza activities, we isolated the three flavonoids, 6-hydroxyluteolin 7-O-β-d-glucoside (1), nepitrin (2), homoplantaginin (3) from the MeOH extract of Salvia plebeia R.Br. and identified them by comparing the spectroscopic data with that reported in the literature. The contents of the three flavonoids in the whole extract were 108.74 ± 0.95, 46.26 ± 2.19, and 69.35 ± 1.22 mg/g for 6-hydroxyluteolin 7-O-β-d-glucoside, nepitrin, and homoplantaginin, respectively, which demonstrates that they are the major constituents of this plant. The three flavonoids were evaluated for their inhibitory activities against influenza virus H1N1 A/PR/9/34 neuraminidase and H1N1-induced cytopathic effect (CPE) on Madin-Darby canine kidney (MDCK) cells. Our results demonstrated the following arrangement for their anti-influenza activities: nepitrin (2) > 6-hydroxyluteolin 7-O-β-d-glucoside (1) > homoplantaginin (3). The potent inhibitory activities of these flavonoids against influenza suggested their potential to be developed as novel anti-influenza drugs in the future.

The principal target organ of duck hepatitis A virus type 1 (DHAV-1) is duckling liver, which is an energy-intensive organ and plays important roles in body's energy metabolism and conversion. As the "power house" of the hepatocytes, mitochondria provide more than 90% of the energy. However, mitochondria are much vulnerable to the oxidative stress for their rich in polyunsaturated fatty acids. Although previous researches have demonstrated that DHAV-1 could induce the oxidative stress in the serum of the infected ducklings, no related study on the mitochondria during the pathological process of DVH has been reported by far. To address this issue, we examined the HE stained tissue pathological slices, detected the hepatic SOD, CAT and GPX activities and MDA contents and analyzed the ATP content, mitochondrial ultrastructure and the mitochondrial SOD, GPX activities and MDA content in the liver tissues. The results showed that the hepatic redox status was significantly disturbed so that causing the mitochondrial dysfunction, ATP depletion and mitochondrial oxidative stress during the process of the DHAV-1 infection, and a prescription formulated with Hypericum japonicum flavone, Radix Rehmanniae Recens polysaccharide and Salvia plebeia flavone (HRS), which had been demonstrated with good anti-oxidative activity in serum, could effectively alleviate the hepatic injury and the oxidative stress in liver tissue induced by DHAV-1 thus alleviating the mitochondrial injury and oxidative stress. In a word, this research discovers the oxidative stress induced mitochondrial dysfunction and oxidative stress during the DVH pathological process and demonstrates HRS exerts good anti-oxidative activity in liver tissue to protect mitochondria against reactive oxygen species (ROS).

The aim of this study was to investigate physicochemical changes in Salvia plebeia R. Br. (SPA) upon hot-air drying and blanching. After hot-air drying and blanching, total polyphenol and flavonoid contents were reduced from 96.64 mg and 48.40 mg gallic acid equivalent/g to 29.70 mg and 22.10 mg quercetin equivalent/g, respectively. DPPH radical scavenging activities at 25 μg/mL of SPA were 94.5% for ascorbic acid, 84.3% for hot-air dried SPA, and 59.7% for blanched SPA and there was no significant difference between those of hot-air dried SPA and ascorbic acid as a positive control. Total sugar contents were 7.187% and 6.104% for hot-air dried SPA and blanched SPA, respectively. During the blanching process, sucrose and maltose contents decreased, whereas glucose and fructose contents increased. Glucose and fructose were converted into citric acid in blanched SPA, whereas sucrose and maltose were converted into tartaric acid, malic acid, and succinic acid. Fourteen kinds of amino acids were found, but methionine, lysine, glycine, histidine, and cysteine were absent. The proportion of essential amino acids was 61.76% upon hot-air drying, which was a relatively high amount. In addition, hot-air drying resulted in 1.40 mg/100 g of norvaline as well as 39.00 mg/100 g of GABA, which are non-amino acids. Therefore, Salvia plebeia R. Br. can be used not only as vegetables but also as highly useful and various health functional foods with antioxidant effects and excellent nutrition.

Nine compounds were successfully separated from Salvia plebeia R.Br. using two-step high-speed counter-current chromatography with three elution modes. Elution-extrusion counter-current chromatography was applied in the first step, while classical counter-current chromatography and recycling counter-current chromatography were used in the second step. Three solvent systems, n-hexane/ethyl acetate/ethanol/water (4:6.5:3:7, v/v), methyl tert-butyl ether/ethyl acetate/n-butanol/methanol/water (6:4:1:2:8, v/v) and n-hexane/ethyl acetate/methanol/water (5:5.5:5:5, v/v) were screened and optimized for the two-step separation. The separation yielded nine compounds, including caffeic acid (1), 6-hydroxyluteuolin-7-glucoside (2), 5,7,3',4'-tetrahydroxy-6-methoxyflavanone-7-glucoside (3), nepitrin (4), rosmarinic acid (5), homoplantaginin (6), nepetin (7), hispidulin (8), and 5,6,7,4'-tertrahydroxyflavone (9). To the best of our knowledge, 5,7,3',4'-tetrahydroxy-6-methoxyflavanone-7-glucoside and 5,6,7,4'-tertrahydroxyflavone have been separated from Salvia plebeia R.Br. for the first time. The purities and structures of these compounds were identified by high-performance liquid chromatography, electrospray ionization mass spectrometry, (1)H and (13)C NMR spectroscopy. This study demonstrates that high-speed counter-current chromatography is a useful and flexible tool for the separation of components from a complex sample.

A phytochemical investigation to obtain new NO inhibitors resulted in the identification of six new (1–6) and four known (7–10) terpenoids from Salvia plebeia. Compounds 1 and 2 are new diterpenoids, 3–5 are new meroditerpenoids, 6–9 are sesquiterpenoids, and 10 is a known meroditerpenoid. The structures of these isolates were determined by routine NMR experiments and X-ray diffraction, as well as the electronic circular dichroism spectra. Compounds 1–4 are diterpenoids carrying an oxygen bridge, and 6 is a rare copane-type sesquiterpenoid with a bridged tricyclic framework. The isolates inhibited NO generation induced by lipopolysaccharide in BV-2 cells. The possible mechanism of NO inhibition of some bioactive compounds was also investigated using molecular docking, which revealed interactions of bioactive compounds with the iNOS protein.

Background The roots of Korean red ginseng (Panax ginseng C.A.Mey.; KGC) have been used as an herbal supplement to enhance vital energy and immune capacity. Salvia plebeia R.Br. has been used to treat inflammatory diseases. Purpose The aim of this study was to examine the anti-asthmatic effects of a mixture of Korean red ginseng and Salvia plebeia R.Br. (KGC3P), its component nepetin, and their modes of action in alleviating ovalbumin (OVA)-induced asthma in mice. Method BALB/c mice were sensitized with OVA then subjected to intratracheal, intraperitoneal, and aerosol challenges. KGC3P and nepetin were administered orally for four weeks. Airway hyperresponsiveness (AHR), OVA-specific IgE levels, and Th2 cytokine- and gene expression levels in bronchoalveolar lavage fluid (BALF) and splenocytes were measured. Histological and immune cell subtype analyses were performed. PTEN and Akt phosphorylation levels were also evaluated. Results KGC3P reduced OVA-induced AHR, serum IgE levels, histological changes, and eosinophils infiltration but also the absolute number of immune cell subtypes including CD3+/CD4+, CD3+/CD8+, CD4+/CD69+, and Gr-1+/CD11b+ in the lungs, BALF, and mesenteric lymph nodes (MLN). KGC3P also lowered the Th2 cytokines IL-4, IL-5, and IL-13 in the BALF and splenocytes and downregulated the IL-4, IL-13, IL-17, TNF-α, and MUC5AC genes in the lung. KGC3P upregulated the peroxisome proliferator-activated receptor (PPAR)γ gene but downregulated the p-Akt and p-PTEN phosphorylation. Similar results were obtained with nepetin treatment. Conclusion KGC3P and nepetin are anti-asthmatic because they reduce various immune cells such as eosinophils and Th2 cell as well as Th2 cytokines. These mechanisms may be accompanied by the regulation of PPARγ expression and the PTEN pathway. Taken together, our results indicate that KGC3P and nepetin may potentially prevent and treat asthma.

Thirty essential oils from higher plants of Gorakhpur Division (India) were evaluated at 0.36 μl/ml against two pulse beetles, Callosobruchus chinensis L. and C. maculatus F., causing infestation of pigeon pea seeds during storage. Clausena pentaphylla oil was more effective and exhibited absolute repellency against both the insects followed by Ocimum canum, Salvia plebeia and Zingiber zerumbet oils. Among these four oils, C. pentaphylla oil was most toxic and showed 100% mortality of both the insects at 10-μl dosage and 24-h exposure (LD50 = 2.7 μl for C. chinensis & 2.4 μl for C. maculatus). Physical factors, viz. temperature, storage and autoclaving, did not cause any adverse effect on the toxicity of Clausena oil. During in vivo investigation, the oil protected 1 kg of pigeon pea seeds completely without reducing weight loss and seed damage up to 6 months when stored in gunny bags and glass containers. The oil was standardised by determining its various physicochemical properties. Thus, C. pentaphylla...

Ethnopharmacological relevance Salvia plebeia R. Br. is an edible plant widely spread in many countries. It has been used as a traditional medicine to treat common cold, flu, cough, hepatitis, hemorrhoids, etc. The purpose of the study is to explicate antiviral compounds responsible for its traditional use for the common cold or flu. Materials and methods The methanolic extract of the aerial parts of S. plebeia was extracted with CHCl3, EtOAc, and n-BuOH, successively. The EtOAc and CHCl3 fractions were subjected to a successive of chromatographic method, which led to the isolation of fourteen compounds. Inhibition activities of the isolated compounds were evaluated against influenza A (H1N1) neuraminidase. Results Chemical investigation of the methanolic extracts of S. plebeia resulted in the isolation of two novel benzoylated monoterpene glycosides, named as plebeiosides A (1) and B (2), together with twelve known compounds including four flavonoids (4–5, 7, 10), two sesquiterpenoids (8, 12), four phenolics (9–10, 13–14), a steroid (6), and a triterpenoid (3). Their chemical structures were elucidated based on spectroscopic data and absolute stereochemistries of 1 and 2 were determined by comparison of optical rotations of their hydrolysates with literature values. Compounds 5, 7, 9, and 11 exhibited potent enzymatic inhibition against H1N1 neuraminidase (IC50 values ranging from 11.18±1.73 to 19.83±2.28 μM). Furthermore, two flavonoids (5 and 7) and one rosmarinic acid methyl ester (9) reduced cytopathic effects of the H1N1 virus during replication. Conclusions The antiviral activities of the flavonoids and phenolics isolated from the extracts of S. plebeia supported the traditional application of this medicine on common cold or flu. In this study, benzoylated monoterpene glycosides were first found to exist in this species. Moreover, the present study suggested potential of three compounds (5, 7, and 9) to be new lead structures for the development of new neuraminidase inhibitors in the future.

The purpose of the present paper was to study the pharmacokinetic characteristics of homoplantaginin, a major active ingredient of Salvia plebeia R.Br. In this study, the effective partition coefficient, in situ absorption in rat intestinal segments and in vitro biotransformation of homoplantaginin by rat intestinal bacteria were determined. In addition, homoplantaginin was administered to rats by intravenous, peritoneal injection and oral administration. The concentrations of homoplantaginin and hispidulin, a metabolite of homoplantaginin, were determined by a validated highperformance liquid chromatographic (HPLC) assay. After intravenous, peritoneal injection, the concentration of hispidulin could not be determined. In contrast, after oral administration, hispidulin and homoplantaginin were simultaneous quantified, homoplantaginin was rapidly absorbed (Tmax=16.00±8.94min), reaching a mean Cmax between 0.77 and 1.27nmol/mL. The absolute oral bioavailability was calculated to be only 0.75%, and the area under curve (AUC) of hispidulin was about 5.4 times than that of homoplantaginin. The poor oral bioavailability may be attributed to the biotransformation of homoplantaginin by rat intestinal bacteria.

Because polysaccharide and flavone ingredients display good antiviral activity, we developed a flavone/polysaccharide-containing prescription that would be effective against duck viral hepatitis (DVH) and investigated its hepatoprotective effects. Flavones were derived from Hypericum japonicum (HJF) (entire herb of Hypericum japonicum Thunb) and Salvia plebeia (SPF) (entire herb of Salvia plebeia R. Br.), and polysaccharides were derived from Radix Rehmanniae Recens (RRRP) (dried root of Rehmannia glutinosa Libosch). This prescription combination was based on the theory of syndrome differentiation and treatment in traditional Chinese veterinary medicine. In vitro and in vivo experiments were conducted using the three single ingredients compared to the combined HRS prescription to determine their anti-duck hepatitis A viral (anti-DHAV) activity. The results showed that all experimental conditions displayed anti-DHAV activity, but the HRS prescription presented the best effect. To further investigate the hepatoprotective effect of the HRS prescription on DHAV-induced hepatic injury, we tested the mortality rate, the hepatic pathological severity score, plasma biochemical indexes of hepatic function, blood DHAV gene expression levels and peroxidation damage evaluation indexes and then analyzed correlations among these indexes. The results demonstrated that the HRS prescription significantly decreased the mortality rate, reduced the severity of hepatic injury, decreased the hepatic pathological severity score, depressed blood DHAV gene expression levels, and returned the indexes of hepatic function and peroxidation almost to a normal level. These results indicate that the HRS prescription confers an outstanding hepatoprotective effect, and we expect that it will be developed into a new candidate anti-DHAV drug.

The purpose of this study was to investigate the effect of the water-soluble polysaccharide-rich sage weed (Salvia plebeia) extracts on intestinal function. The results showed that the extract is rich in water-soluble polysaccharides (60.5/100 g extract), which are mainly composed of pectic polysaccharides and hemicellulose. The inclusion of sage weed extract in the control diet at a level of 0.5/100 g diet resulted in significantly (P d -glucuronidase, β- d -glucosidase, mucinase, and urease. These findings suggest that an adequate intake of sage weed extracts (0.5/100 g diet) may play a role in the maintenance of intestinal health by reducing the exposure of intestinal mucosa to toxic materials and other harmful compounds.

Salvia plebeiaR. Br. (Labiatae), distributed in many countries such as Korea, China, India, Iran, and Australia, is used as a folk remedy for a variety of inflammatory diseases including hepatitis, cough, diarrhea, gonorrhea, menorrhagia, tumors, and hemorrhoids. This study focused on determining the involvement of anti-inflammatory heme oxygenase-1 (HO-1) in the inhibitory activity of an extract of Salvia plebeiaR. Br. leaves (SPL) on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in lipopolysaccharide (LPS)- stimulated RAW264.7 macrophages. SPL extract at the highest concentration (500 μg/mL) significantly inhibited NO production by approximately 85% and suppressed iNOS protein expression by approximately 90% compared to LPS-stimulated cells. The SPL extract induced the expression of HO-1 in a dose-dependent manner, and blocking HO-1 activity abolished the inhibitory effects of the SPL extract on NO production. These results suggest that an SPL extract has potent anti-inflammatory activity through HO-1 induction in RAW264.7 macrophages.

The antioxidant potential and enzyme activities in Salicornia herbacea, Corylopsis coreana, Erythronium japonicum, Phragmites communis, Momordica Charantia, Nelumbo nucifera, Salvia plebeia, Portulaca oleracea, Ficus carica, Citrus junos and Cornus officinalis were determined. Their antioxidant activities were measured using DPPH radical scavenging and nitrite scavenging activity. Enzyme activities in investigated plants were evaluated as superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and ascorbate peroxidase (APX). The DPPH scavenging rate from 100 to 2500 mgL-1 was the highest in the flower of Corylopsis coreana. However, it was not detected in most of the samples at concentration below 100 mgL-1. The nitrite scavenging activity according to each kind of resource plants was significantly higher in the stem of Corylopsis coreana and leaf of Nelumbo nucifera.. The root extract of Erythronium japonicum had the highest SOD enzyme activity of 94.0% while leaf of Salvia plebeia showed the lowest SOD enzyme activity of 30.4%. The activity of CAT and APX showed higher values in the stem of Corylopsis coreana, root of Erythronium japonicum and root of Phragmites communis in comparison with other plants. The activity of POD showed significantly high values in stem of Corylopsis coreana, Momordica Charantia and pericarp of Citrus junos extracts. The antioxidant enzyme activities differ significantly in different plants. In conclusion, we showed that Corylopsis coreana, Erythronium japonicum Cornus officinalis, and Momordica Charantia had the potent biological activities. Therefore, these plant resources showing antioxidant activity could be good materials for development of source of functional healthy food.

Aim of the study Compound Salvia Plebeia Granules (CSPG) had been used for treating urinary tract infection (UTI) for more than 20 years in Drum Tower hospital, but there were lack of sufficient pharmacology studies. The aim of this study was to testify the effects of CSPG on UTI, namely to prove its diuretic, antiblastic, antipyretic and antidynous activities. Materials and methods This study evaluated the diuretic effect of CSPG on water load Sprague–Dawley (SD) male rats by the method of metabolic cage, and then analysed the contents of Na + , K + , and Cl − in urine. The antiblastic activity of CSPG was testified by various kinds of strains in vitro . The antipyretic effect was evaluated by carrageenan-induced fever model in mice. Antidynous activity was demonstrated by the method of acetic acid-induced writhing. Results Intragastric (i.g.) administration of CSPG (20–40 g/kg) (equivalent to crude herb) produced a dose-related diuretic effect on water load mice and promoted excreting of Na + , K + , and Cl − in urine. In addition, the minimal inhibitory concentrations (MICs) of CSPG on Escherichia coli and Staphylococcus aureus were separately 0.25 g/ml and 0.5 g/ml. Moreover, i.g. the doses of CSPG ranging from 25.2 to 50.4 g/kg showed significantly antipyretic effect on carrageenan-induced fever in mice. CSPG (12.6–50.4 g/kg) can also produce dose-related antidynous effects on acetic acid-induced writhing in mice. Conclusions The results described the integrity report of pharmacological studies of CSPG and indicated that it had significantly diuretic, antiblastic, antipyretic, anti-inflammatory and antidynous activities which support its folk medicine use on UTI.

This study was designed to investigate the effect of Plebeiae Herba (Salvia plebeia R. Br.) on the proliferation of AGS cell lines and the activation of splenocytes. In an anti-cancer test using AGS cells, water and ethanol extracts of Plebeiae Herba inhibited the growth of AGS cell lines and morphological changes were also observed in a dose-dependent manner. Water extract of Plebeiae Herba showed growth-inhibitory effect of 43.3% at 1,000 ㎍/mL and 69.7% at 3,000 ㎍/mL. Ethanol extracts of Plebeiae Herba showed growth-inhibitory effect of approximately 37.3% for 1,000 ㎍/mL and 75.8% for 3,000 ㎍/mL. The Plebeiae Herba induced the proliferation of spleen cells and increased interleukin (IL)-2, interleukin (IL)-6 and tumor necrosis factor (TNF)-α. In conclusion, these results suggest that the Plebeiae Herba seems to have antiproliferationg effect against the AGS cell and acts as a potent immunomodulator.