BACKGROUND: A disruption of the balance between the water content of the stratum corneum (SC) and skin surface lipids may lead to the clinical manifestation of dryness of skin in patients with atopic dermatitis (AD). OBJECTIVE: To determine whether supplementation of gromwell (Lithospermum erythrorhizon), one of herbs used in East Asia in remedies for various abnormal skin conditions, may improve the SC level of hydration and ceramides, major lipid in SC in patients with AD. METHODS: A total of 28 subjects with AD were randomly assigned into two groups: either gromwell group received dextrose contained capsules with 1.5 g of gromwell extracts or placebo group received only dextrose contained capsules for 10 weeks. RESULTS: In contrast to no alteration of SC hydration and ceramides in placebo group, the SC hydration in gromwell group was significantly increased in parallel with an increase of SC ceramides. Furthermore, % increase of SC hydration in gromwell group bore a positive correlation with the clinical severity, which suggests that the increase of SC hydration in gromwell group was more effective as AD was more severe. CONCLUSION: Supplementation of gromwell improves SC hydration in parallel with an increase of ceramides in part.
Capsules ; Ceramides ; Dermatitis, Atopic ; Far East ; Glucose ; Humans ; Lithospermum ; Skin

DF formula is comprised of three traditional herbs, Ephedra intermedia, Rheum palmatum and Lithospermum erythrorhizon, and locally used for treating of the metabolic diseases, such as obesity and diabetes in Korea. We tried to optimize the extraction conditions of two major components, (−)-ephedrine and (+)-pseudoephedrine, in DF formula using response surface methodology with Box-Behnken design (BBD). The experimental conditions with 70% for EtOH concentrations, 4.8 hour for extraction hours and 8.7 times for the solvent to material ratio were suggested for the optimized extraction of DF formula with the highest amounts of (−)-ephedrine and (+)-pseudoephedrine in the designed model.
Chromatography, High Pressure Liquid ; Ephedra ; Korea ; Lithospermum ; Metabolic Diseases ; Obesity ; Rheum

Shikonin, a natural flavonoid found in the roots of Lithospermum erythrorhizon, has been shown to possess many biological functions. The present study was undertaken to investigate the influence of shikonin on vascular smooth muscle contractility and to determine the mechanism involved. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Shikonin significantly relaxed fluoride-, thromboxane A2- or phorbol ester-induced vascular contraction suggesting as a possible anti-hypertensive on the agonist-induced vascular contraction regardless of endothelial nitric oxide synthesis. Furthermore, shikonin significantly inhibited fluoride-induced increases in pMYPT1 levels and phorbol ester-induced increases in pERK1/2 levels suggesting the mechanism involving the inhibition of Rho-kinase activity and the subsequent phosphorylation of MYPT1 and the inhibition of MEK activity and the subsequent phosphorylation of ERK1/2. This study provides evidence regarding the mechanism underlying the relaxation effect of shikonin on agonist-induced vascular contraction regardless of endothelial function.
Animals ; Fluorides ; Humans ; Isometric Contraction ; Lithospermum ; Male ; Muscle, Smooth, Vascular ; Nitric Oxide ; Phosphorylation ; Rats ; Relaxation ; rho-Associated Kinases

According to the expansion of lifespan, neuronal disorder based on inflammation has been social problem. Therefore, we isolated shikonin from Lithospermum erythrorhizon and evaluated anti-inflammatory effects of shikonin in lipopolysaccharide (LSP)-stimulated BV2 microglial cells. Shikonin dose-dependently inhibits the expression of the proinflammatory mediators, nitric oxide (NO), prostaglandin E2 (PGE2), and tumor necrosis factor-alpha (TNF-alpha) as well as their main regulatory genes and products such as inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and TNF-alpha in LPS-stimulated BV2 microglial cells. Additionally, shikonin suppressed the LPS-induced DNA-binding activity of nuclear factor-kappaB (NF-kappaB) to regulate the key regulatory genes of the proinflammatory mediators, such as iNOS, COX-2, and TNF-alpha, accompanied with downregulation of reactive oxygen species (ROS) generation. The results indicate that shikonin may downregulate the expression of proinflammatory genes involved in the synthesis of NO, PGE2, and TNF-alpha in LPS-treated BV2 microglial cells by suppressing ROS and NF-kappaB. Taken together, our results revealed that shikonin exerts downregulation of proinflammatory mediators by interference the ROS and NF-kappaB signaling pathway.
Cyclooxygenase 2 ; Dinoprostone ; Down-Regulation ; Genes, Regulator ; Inflammation ; Lithospermum* ; Neurons ; NF-kappa B* ; Nitric Oxide ; Nitric Oxide Synthase ; Reactive Oxygen Species* ; Social Problems ; Tumor Necrosis Factor-alpha

Methanol and/or boiling water extraction of 201 natural products and subsequent MTT assay using MT-4 cell line was carried out to screen the anti-HIV-1 activity. Among 97 methanol extracts, 7 extracts from Chrysanthemi Indicium Flos, Magnoliae Cortex Machili Cortex, Reynoutriae Rhizoma, Lithospermi Radix Agastachis Herba, and Chaenomelis Fructus showed anti-HIV-1 activity and their SI value were 2.25 to 5.77. In addition, among 119 boiling water extracts, 10 extracts from Lonicerae Caulis et Foloium, Elsholtziae Herba, Leonuri Herba, Portulacae Herba, Schizonepetae Herba, Curcumae Rhizoma, Amomi Cardamomi Fructus, Cirsii Radix et Herba, Carpesii Herba, and Siegesbeckiae Herba showed anti-HIV-1 activity and their SI value were 1.30 to 7.64. Methanol extracts of above seven natural products were fractionated and the anti-HRs_1 activity of each fraction was examined. Extraction was carried out with hexane, chloroform, butanol, and water to trace active anti-HIV-1 componets. As a result, the water fraction of Magnoliae Cortex, Machili Cortex, Reynoutriae Rhizoma, Agastachis Herba, Chaenomelis Fructus and the butanol fraction of Chrysanthemi Indicium Flos, Reynoutriae Rhizoma showed anti-HIV-1 activity and their SI value were 1.40 to 8.02. We could reach a conclusion that studies to trace the anti-HIV-1 active component of each natural products in further Sractionation and to identify its structure by Infrared spectroscopy, NMR spectroscopy and gel permeation chromatography were needed.
Biological Products ; Cell Line ; Chloroform ; Chromatography, Gel ; Curcuma ; Lamiaceae ; Lithospermum ; Lonicera ; Magnetic Resonance Spectroscopy ; Magnolia ; Mass Screening* ; Methanol ; Portulaca ; Spectrum Analysis ; Water

OBJECTIVETo evaluate the effectiveness and safety of lyophilized Salvia salt of lithospermic acid powder for injection (SSLA) in treating coronary heart diseases angina pectoris (CHD-AP) of Xin-blood stasis syndrome type, and to conduct the non-inferiority trial with Danshen injection (DSI) as positive control.

METHODSAn non-inferiority clinical layered, segmented, randomized, and blinded trial on three parallel and multiple centered groups was conducted in 480 patients with stable effort angina grade I, II and III, who had two or more times of attack every week. The 240 patients in test group A were treated with SSLA 200 mg added in 250 ml of 5% glucose solution for intravenous dripping every day; the 120 patients in test group B were treated with SSLA but the dosage doubled; and the 120 patients in the control group were treated with DSI 20 ml daily in the same method as SSLA was given. The clinical effectiveness and safety were evaluated after the patients were treated for 14 days.

RESULTSThe results showed that the markedly effective rate in test groups A, B and control group was 37.45%, 36.75% and 30.09% respectively, while the total effective rate in them was 88.09%, 89.74% and 67.26% respectively. Statistical significance was shown in comparisons of the therapeutic effect between control group with test group A and test group B, with that in the two test groups superior to that in the control group, and non-inferiority trial showed eligibility (P < 0.01). Adverse reaction appeared in 8 patients in the test groups and 2 in the control group.

CONCLUSIONSSLA has definite therapeutic effect in treating patients with CHD-AP, with its effect not inferior to that of DSI, and no evident toxic-adverse reaction.

Adolescent ; Adult ; Aged ; Angina Pectoris ; drug therapy ; Benzofurans ; adverse effects ; therapeutic use ; Depsides ; Double-Blind Method ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Freeze Drying ; Humans ; Infusions, Intravenous ; Lithospermum ; Male ; Middle Aged ; Phytotherapy ; Salvia ; Salvia miltiorrhiza ; adverse effects

Shikonin, which derives from Lithospermum erythrorhizon, has been traditionally used against a variety of diseases, including cancer, in Eastern Asia. Here we determined that shikonin inhibits proliferation of gastric cancer cells by inducing apoptosis. Shikonin's biological activity was validated by observing cell viability, caspase 3 activity, reactive oxygen species (ROS) generation, and apoptotic marker expressions in AGS stomach cancer cells. The concentration range of shikonin was 35–250 nM with the incubation time of 6 h. Protein levels of Nrf2 and p53 were evaluated by western blotting and confirmed by real-time PCR. Our results revealed that shikonin induced the generation of ROS as well as caspase 3-dependent apoptosis. c-Jun-N-terminal kinases (JNK) activity was significantly elevated in shikonin-treated cells, thereby linking JNK to apoptosis. Furthermore, our results revealed that shikonin induced p53 expression but repressed Nrf2 expression. Moreover, our results suggested that there may be a co-regulation between p53 and Nrf2, in which transfection with siNrf2 induced the p53 expression. We demonstrated for the first time that shikonin activated cell apoptosis in AGS cells via caspase 3- and JNK-dependent pathways, as well as through the p53-Nrf2 mediated signal pathway. Our study validates in partly the contribution of shikonin as a new therapeutic approaches/ agent for cancer chemotherapy.
Apoptosis ; Blotting, Western ; Caspase 3 ; Cell Death* ; Cell Survival ; Drug Therapy ; Far East ; Humans* ; Lithospermum ; Phosphotransferases ; Reactive Oxygen Species ; Real-Time Polymerase Chain Reaction ; Signal Transduction ; Stomach Neoplasms ; Stomach* ; Transfection

A nucleoside diphosphate-linked moiety X (Nudix) hydrolase-like gene, YSA1, has been identified as one of the gromwell plant extract-responsive genes in Cryptococcus neoformans. Ysa1 is known to control intracellular concentrations of ADP-ribose or O-acetyl-ADP-ribose, and has diverse biological functions, including the response to oxidative stress in the ascomycete yeast, Saccharomyces cerevisiae. In this study, we characterized the role of YSA1 in the stress response and adaptation of the basidiomycete yeast, C. neoformans. We constructed three independent deletion mutants for YSA1, and analyzed their mutant phenotypes. We found that ysa1 mutants did not show increased sensitivity to reactive oxygen species-producing oxidative damage agents, such as hydrogen peroxide and menadione, but exhibited increased sensitivity to diamide, which is a thiol-specific oxidant. Ysa1 was dispensable for the response to most environmental stresses, such as genotoxic, osmotic, and endoplasmic reticulum stress. In conclusion, modulation of YSA1 may regulate the cellular response and adaptation of C. neoformans to certain oxidative stresses and contribute to the evolution of antifungal drug resistance.
Adenosine Diphosphate Ribose ; Ascomycota ; Basidiomycota ; Cryptococcus neoformans* ; Cryptococcus* ; Diamide ; Drug Resistance, Fungal ; Endoplasmic Reticulum Stress ; Hydrogen Peroxide ; Lithospermum ; O-Acetyl-ADP-Ribose ; Oxidative Stress* ; Oxygen ; Phenotype ; Plants ; Saccharomyces cerevisiae ; Vitamin K 3 ; Yeasts

OBJECTIVETo study the effects of lithospermum extract on MCF-7 cell and estrogen and progestogen levels in mice.

METHODCell growth curve and Western Blotting were used to do animal experiment.

RESULTLithospermum extract could inhibit the growth of MCF-7 cell. It could also inhibit the expression of ER and increase the expression of PR with large dose. After the mice were bred with Lithospermum, their serum estrogen and progestogen levels reduced, their uterus weight index decresed and uterus ER and PR levels increased. It could also improve the hyperplasia of uterus caused by tamoxifen.

CONCLUSIONLithospermum extract can inhibit the growth of MCF-7 cell and inhibit the level of estrogen and progestogen in mice.

Animals ; Breast Neoplasms ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacology ; Estrogens ; blood ; Female ; Humans ; Hyperplasia ; chemically induced ; Lithospermum ; chemistry ; Mice ; Mice, Inbred BALB C ; Plants, Medicinal ; chemistry ; Progestins ; blood ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Tamoxifen ; adverse effects ; Uterus ; metabolism ; pathology

Shikonin, the main active ingredient of Lithospermum, and its derivatives have been proved to have antitumor effects, and the anti-tumor mechanisms involve multiple targets. Based on recent literatures, this review focuses on the antitumor effects and its mechanisms. More emphases are given on the aspects of induction of apoptosis, induction of necrosis, acting on matrix metalloproteinase, acting on the protein tyrosine kinase and antiangiogenesis. The current status and problems of shikonin derivatives in antitumor effects are simply summarized and lookout for the development of antitumor drugs with shikonin as leading compounds.
Antineoplastic Agents, Phytogenic ; isolation & purification ; pharmacology ; therapeutic use ; Apoptosis ; drug effects ; Cell Line, Tumor ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; therapeutic use ; Humans ; Lithospermum ; chemistry ; Matrix Metalloproteinase 9 ; metabolism ; Naphthoquinones ; isolation & purification ; pharmacology ; therapeutic use ; Necrosis ; Neoplasms ; drug therapy ; metabolism ; pathology ; Neovascularization, Pathologic ; prevention & control ; Plants, Medicinal ; chemistry ; Protein-Tyrosine Kinases ; metabolism ; Reactive Oxygen Species ; metabolism