Stigmasterol is a plant sterol with anti-apoptotic, anti-oxidative and anti-inflammatory effect through multiple mechanisms. In this study, we further assessed whether it exerts protective effect on human brain microvessel endothelial cells (HBMECs) against ischemia-reperfusion injury and explored the underlying mechanisms. HBMECs were used to establish an in vitro oxygen and glucose deprivation/reperfusion (OGD/R) model, while a middle cerebral artery occlusion (MCAO) model of rats were constructed. The interaction between stigmasterol and EPHA2 was detected by surface plasmon resonance (SPR) and cellular thermal shift assay (CETSA). The results showed that 10 μmol·L^-1 stigmasterol significantly protected cell viability, alleviated the loss of tight junction proteins and attenuated the blood-brain barrier (BBB) damage induced by OGD/R in thein vitro model. Subsequent molecular docking showed that stigmasterol might interact with EPHA2 at multiple sites, including T692, a critical gatekeep residue of this receptor. Exogenous ephrin-A1 (an EPHA2 ligand) exacerbated OGD/R-induced EPHA2 phosphorylation at S897, facilitated ZO-1/claudin-5 loss, and promoted BBB leakage in vitro, which were significantly attenuated after stigmasterol treatment. The rat MCAO model confirmed these protective effects in vivo. In summary, these findings suggest that stigmasterol protects HBMECs against ischemia-reperfusion injury by maintaining cell viability, reducing the loss of tight junction proteins, and attenuating the BBB damage. These protective effects are at least meditated by its interaction with EPHA2 and inhibitory effect on EPHA2 phosphorylation.
Humans ; Animals ; Rats ; Stigmasterol ; Phosphorylation ; Endothelial Cells ; Molecular Docking Simulation ; Reperfusion Injury ; Blood-Brain Barrier ; Glucose ; Microvessels ; Oxygen

A contributory role of oxidative stress and protection by antioxidant nutrients have been suspected in cataract formation. Ganoderic acid A (GAA), an effective lanostane triterpene, is widely reported as an antioxidant. The aim of this study is to investigate the potential effects of GAA on cataract formation. After lens epithelial cells (LECs) were exposed to UVB radiation for different periods, cell viability, apoptosis-related protein levels, malondialdehyde (MDA) and superoxide dismutase (SOD) activities were monitored. We found that cell viability, the Bcl-2/Bax ratio and SOD activity were increased, while Cleaved caspase-3 levels and MDA activity were decreased compared with those in UVB-impaired LECs after GAA treated. Furthermore, GAA activated PI3K/AKT in UVB-impaired LECs and effectively delayed the occurrence of lens opacity in vitro. In conclusion, these findings demonstrated that GAA exhibited protective functions in SRA01/04 cells and rat lenses against UVB-evoked impairment through elevating cell viability and antioxidant activity, inhibiting cell apoptosis, activating the PI3K/AKT pathway and delaying lens opacity.
Animals ; Apoptosis ; Cataract/prevention & control* ; Cell Line ; Cell Survival ; Epithelial Cells/radiation effects* ; Heptanoic Acids/pharmacology* ; Humans ; Lanosterol/pharmacology* ; Lens, Crystalline/radiation effects* ; Malondialdehyde/metabolism* ; Rats ; Superoxide Dismutase/metabolism* ; Ultraviolet Rays/adverse effects*

Ganoderic acid(GA) is one of main bioactive components produced by Ganoderma lucidum,which a traditional Chinese herbal medicine and a kind of tracyclic triterpene lanosterol derivatives with highly oxidized structure. It has a variety of important pharmacological activities,such as anticancer,immunoregulation,anti-oxidation,anti-diabetes and anti-HIV. At present,the studies of GA mainly focus on biosynthesis,fermentation control,isolation and purification,structure identification and pharmacological effects.However,there are a fewer pharmacokinetic studies of GA,although it is closely related to the clinical application. Recent studies have shown that GA can be absorbed rapidly by gastrointestinal tract and distributed in various tissues and organs after oral intake. GA is metabolized by liver at phase Ⅰ and phase Ⅱ,and then mainly excreted by bile. In this paper,the pharmacokinetic characteristics of GA and its absorption,distribution,metabolism and excretion(ADME) will be systematically summarized,in order to provide scientific basis for the application and development studies of Ganoderma triterpenoid drugs and their rational clinical use.
Humans ; Lanosterol ; pharmacokinetics ; Reishi ; chemistry ; Triterpenes ; pharmacokinetics

This study analyzed the seeds of Zizyphus jujuba var. inermis commonly used as a remedy in traditional Chinese medicine, in order to determine its various biologically active compounds. Through process 3-pentadecylcatechol, ρ-menth-8-ene, and γ-bisabolene were isolated and identified for the first time which are urushiol, monoterpenoidal, and sesquiterpenoidal compounds, respectively. Also, found were another sesquiterpenoidal compounds, vomifoliol, and four steroidal compounds, β-sitosterol, stigmasterol, stigmasta-5,23-dien-3β-ol, and stigmast-4-en-3-one. In addition, fourteen triterpenoidal compounds were isolated and identified. These were lupeol, betulinic acid, betulinaldehyde, alphitolic acid, 3-O-cis-ρ-coumaroyl-alphitolic acid, 3-O-trans-ρ-coumaroylalphitolic acid, 2-O-cis-ρ-coumaroyl-alphitolic acid, 2-O-trans-ρ-coumaroyl-alphitolic acid, zizyberanalic acid, ceanothic acid, oleanolic acid, maslinic acid, 3-O-cis-ρ-coumaroyl-maslinic acid, and 3-O-trans-ρ-coumaroylmaslinic acid. The structures were identified by comparing of the spectroscopic experiments, NMR and MS, and then compared that reported data, respectively. Three extracts of water, methanol, and chloroform from the seeds showed a weak anti-proliferative effect, anti-microbial activity, and anti-oxidant effect, respectively.
Antioxidants ; Chloroform ; Medicine, Chinese Traditional ; Methanol ; Oleanolic Acid ; Stigmasterol ; Water ; Ziziphus*

BACKGROUND: Skin flap necrosis is a common complication after mastectomy and breast reconstruction. It has been proven that nitroglycerin ointment, as a topical vasodilator, can decrease the rate of skin flap necrosis after mastectomy and breast reconstruction. However, nitroglycerin can cause several side effects, including headache, dizziness, and hypotension. The purpose of this study was to evaluate whether the application of a low dose of nitroglycerin ointment reduced the rate of skin flap necrosis in breast reconstruction after skin-sparing or nipple-sparing mastectomy. METHODS: A total of 73 cases of breast reconstruction after nipple-sparing and skin-sparing mastectomy at our institution from March 2012 to January 2017 were retrospectively studied. Of these patients, 52 received nitroglycerin ointment (4.5 mg) application to the skin around the nipple-areolar complex from August 2015 to January 2017, while 21 received fusidic acid ointment from March 2012 to August 2015. The number of patients who experienced necrosis of the breast skin flap was counted in both groups. RESULTS: Skin flap necrosis developed in 2 (3.8%) patients who were treated with nitroglycerin ointment and 5 (23.8%) patients who did not receive nitroglycerin ointment treatment. Patients who did not receive nitroglycerin ointment treatment had a significantly higher risk of mastectomy skin flap necrosis than patients who did (odds ratio=7.81; 95% confidence interval, 1.38 to 44.23; P=0.02). CONCLUSIONS: Low-dose nitroglycerin ointment administration significantly decreased the rate of skin flap necrosis in patients who underwent breast reconstruction after skin-sparing or nipple-sparing mastectomy, without increasing the incidence of the side effects of nitroglycerin.
Breast* ; Dizziness ; Female ; Fusidic Acid ; Headache ; Humans ; Hypotension ; Incidence ; Mammaplasty* ; Mastectomy* ; Necrosis* ; Nitroglycerin* ; Ointments ; Retrospective Studies ; Skin*

The present study aimed to study lipid-lowering effect of seven traditional Chinese medicine monomers in zebrafish system. Zebrafish were fed with high fat diet to establish a hyperlipemia model, then fasted and bathed with seven traditional Chinese medicine monomers stigmasterol, triacontanol, chrysophanol, vanillic acid, shikimic acid, polydatin and oleanolic acid respectively. The oil red O staining was used to detect the blood lipids of zebrafish. Serum total cholesterol and triglyceride levels were detected to validate the lipid-lowering effect. The result showed that a zebrafish model of hyperlipemia could be established by feeding larvae zebrafish with high fat diet. Among the seven traditional Chinese medicine monomers, chrysophanol had lipid-lowering effect. Chrysophanol significantly reduced serum total cholesterol and triglyceride levels in adult zebrafish fed with high fat diet. Chrysophanol accelerated peristalsis frequency of zebrafish intestine and the excretion of high fat food. It is concluded that chrysophanol has lipid- lowering effect in zebrafish, and the mechanism of the effect may be due to the roles of chrysophanol in reducing lipid absorption from gastrointestinal tract and accelerating the excretion of food.
Animals ; Anthraquinones ; pharmacology ; Diet, High-Fat ; Fatty Alcohols ; pharmacology ; Glucosides ; pharmacology ; Hyperlipidemias ; drug therapy ; Hypolipidemic Agents ; pharmacology ; Larva ; Lipids ; blood ; Medicine, Chinese Traditional ; Oleanolic Acid ; pharmacology ; Shikimic Acid ; pharmacology ; Stigmasterol ; pharmacology ; Stilbenes ; pharmacology ; Vanillic Acid ; pharmacology ; Zebrafish

Phytochemical investigation on the leaves of Pileostegia viburnoides Hook.f.et Thoms led to the isolation of twenty-five compounds, and their structures were identified as n-dotriacontane (1), taraxeryl acetate (2), friedelin (3), epifriedelinol (4), canophyllal (5), stigmast-4-en-3-one (6), stigmasterol (7), (24R)-5A-stigmastane-3,6-dione (8), ursolic acid (9), pomolic acid (10), umbelliferone (11), 4-epifriedelin (12), n-octatriacontanol (13), β-amyrin (14), α-amyrin (15), taraxerol (16), nonadecanol (17), friedelane (18), arachic acid (19), protocatechuic acid (20), n-pentatriacontanol (21), hexadecanoic acid (22), vincosamide (23), daucosterol (24), and skimming (25), respectively. To our best knowledge, compounds 1, 2, 12, 13, 17 - 19 and 21-23 were new within Saxifragaceae family. Compounds 15, 16, and 20 were produced from this genus for the first time. Compounds 4, 14 and 25 were first obtained from species P. viburnoides and compounds 3, 5 - 11, and 24 were achieved from the leaves of P. viburnoides for the first time. Furthermore, the anti-neuroinflammatory activity of these isolates was evaluated.
Coumarins ; Humans ; Palmitic Acid ; Saxifragaceae ; Stigmasterol ; Triterpenes

BACKGROUND: A small subset of adolescents atopic dermatitis (AD) tends to persist. This also leads to get more antibiotics exposure with advancing years. Antibiotic resistance has been regarded as a serious problem during Staphylococcus aureus treatment, especially methicillin-resistant S. aureus (MRSA). OBJECTIVE: It was investigated the S. aureus colonization frequency in the skin lesions and anterior nares of adolescent AD patients and evaluated the changes in S. aureus antimicrobial susceptibility for years. METHODS: Patients who visited our clinic from September 2003 to August 2005 were classified into group A, and patients who visited from August 2010 to March 2012 were classified into group B. To investigate the differences with regard to patients' age and disease duration, the patients were subdivided into groups according to age. Lesional and nasal specimens were examined. RESULTS: Among the 295 AD patients, the total S. aureus colonization rate in skin lesions was 66.9% (95/142) for group A and 78.4% (120/153) for group B. No significant changes in the systemic antimicrobial susceptibilities of S. aureus strains isolated from adolescent AD patients were observed during about 10-year period. The increased trend of MRSA isolation in recent adolescent AD outpatients suggest that the community including school could be the source of S. aureus antibiotic resistance and higher fusidic acid resistance rates provides evidence of imprudent topical use. CONCLUSION: Relatively high MRSA isolation and fusidic acid resistance rates in recent AD patients suggest that the community harbors antibiotic-resistant S. aureus.
Adolescent ; Anti-Bacterial Agents ; Colon ; Dermatitis, Atopic* ; Drug Resistance, Microbial ; Fusidic Acid ; Humans ; Methicillin Resistance ; Methicillin-Resistant Staphylococcus aureus ; Outpatients ; Skin ; Staphylococcus aureus* ; Staphylococcus*

Community-associated methicillin resistant Staphylococcus aureus (CA-MRSA) has become widespread in the community and healthcare settings, and a number of clonal lineages emerged on every country. Sequence type (ST) 80 clone of CA-MRSA was dominant in Europe and has increasingly been isolated from the Middle East but so far never found in Korea. In this study, 48 MRSA isolates recovered from ear infections were characterized by multilocus sequence typing (MLST), staphylococcal cassette chromosome mec (SCCmec) typing, staphylocoagulase (SC) genotyping, staphylococcal protein A gene (spa) typing, accessory gene regulator (agr) typing, and virulence gene profiling. Most MRSA strains belonged to three major clones: ST5-SCCmec II-SC type II (n=19, 39.6%), ST239-SCCmec III-SC type IV (n=15, 31.2%), and ST72-SCCmec IV-SC type Vb (n=11, 22.9%). Among the isolates, one strain was Panton- Valentine leukocidin (PVL)-positive ST80-SCCmec IV-SC type XIa - spa type t044-agr group III, and exfoliative toxin D-positive. This strain was susceptible to most antibiotics, but resistant to tetracycline and fusidic acid. This is the first report on the emergence of European ST80 CA-MRSA clone in Korea.
Anti-Bacterial Agents ; Busan* ; Clone Cells* ; Coagulase ; Delivery of Health Care ; Ear ; Europe ; Fusidic Acid ; Korea* ; Leukocidins ; Methicillin Resistance* ; Methicillin-Resistant Staphylococcus aureus* ; Middle East ; Multilocus Sequence Typing ; Staphylococcal Protein A ; Staphylococcus aureus ; Tetracycline ; Virulence

BACKGROUND: Clean dermatologic procedures create wounds with a low risk of infection (usually up to 5%). Whether the use of topical antibiotics is advocated, with regard to its efficacy and safety issues such as antibiotic resistance and sensitizing potential, is controversial. Fusidic acid, a topical antibiotic against gram-positive bacteria, is a rare sensitizer and commonly used in postprocedure care in Korea. OBJECTIVE: This is a retrospective study aimed at comparing the efficacy and safety between fusidic acid and petrolatum for the postprocedure care of clean dermatologic procedures. METHODS: Patients were treated with either fusidic acid or petrolatum ointment, applied on the wound created during clean dermatologic procedures such as biopsy of the punch, incisional, excisional, and shave types. The efficacy, adverse events, and subjective level of satisfaction were retrieved from medical records. RESULTS: A total of 414 patients with a total of 429 wounds were enrolled. The overall rate of adverse events was 0.9%, and the rates of adverse events in the fusidic acid group and the petrolatum group were 1.4% and 0.5%, respectively (p=0.370). There was no wound discharge, pain, tenderness, swelling, induration, or dehiscence in both groups. The patients' self-assessment of the wound was not significantly different between the two treatment groups. CONCLUSION: Our findings support the hypothesis that the routine prophylactic use of topical antibiotics is not indicated for clean dermatologic procedures. We recommend the use of petrolatum in the postoperative care of clean dermatologic procedures because of its equivalent efficacy and superior safety profiles.
Anti-Bacterial Agents ; Biopsy ; Dermatologic Surgical Procedures ; Drug Resistance, Microbial ; Fusidic Acid* ; Gram-Positive Bacteria ; Humans ; Korea ; Medical Records ; Petrolatum* ; Postoperative Care ; Retrospective Studies* ; Self-Assessment ; Wound Healing ; Wounds and Injuries