Humans ; Amyotrophic Lateral Sclerosis/drug therapy* ; Benzofurans/therapeutic use* ; Double-Blind Method ; Treatment Outcome

Salvianolic acid B(Sal B), tanshinone Ⅱ_A(TSN Ⅱ_A), and glycyrrhetinic acid(GA) lipid emulsion(GTS-LE) was prepared by the high-speed dispersion method combined with ultrasonic emulsification.The preparation process of the emulsion was optimized by single-factor method and D-optimal method with appearance, centrifugal stability, and particle size of the emulsion as evalua-tion indexes, followed by verification.In vitro release of Sal B, TSN Ⅱ_A, and GA in GTS-LE was performed by reverse dialysis.In vivo pharmacokinetic evaluation was carried out in mice.The acute liver injury model was induced by acetaminophen.The effect of oral GTS-LE on the acute liver injury was investigated by serum liver function indexes and pathological changes in liver tissues of mice.The results showed that under the optimal preparation process, the average particle size of GTS-LE was(145.4±9.25) nm and the Zeta potential was(-33.6±1.45) mV.The drug-loading efficiencies of Sal B, TSN Ⅱ_A, and GA in GTS-LE were above 95%, and the drug release in vitro conformed to the Higuchi equation.The pharmacokinetic results showed that the C_(max) of Sal B, TSN Ⅱ_A, and GA in GTS-LE was 3.128, 2.7, and 2.85 times that of the GTS-S group, and AUC_(0-t) of Sal B, TSN Ⅱ_A, and GA in GTS-LE was 3.09, 2.23, and 1.9 times that of the GTS-S group.After intragastric administration of GTS-LE, the activities of alanine aminotransferase and aspartate aminotransferase were significantly inhibited, the content of malondialdehyde was reduced, and the structure of hepatocytes recovered to normal.In conclusion, GTS-LE can delay the release of Sal B and promote the release of TSN Ⅱ_A and GA.The encapsulation of three drug components in the emulsion can improve the oral bioavailability to varying degrees and can effectively prevent the acute liver injury caused by acetaminophen.
Abietanes/therapeutic use* ; Acetaminophen/therapeutic use* ; Alanine Transaminase/metabolism* ; Animals ; Antipyretics/therapeutic use* ; Aspartate Aminotransferases/metabolism* ; Benzofurans/therapeutic use* ; Chemical and Drug Induced Liver Injury/prevention & control* ; Depsides/therapeutic use* ; Emulsions ; Glycyrrhetinic Acid/therapeutic use* ; Liver/drug effects* ; Malondialdehyde ; Mice

Cerebral ischemia is also known as ischemic stroke. In recent years, research on neuroprotection after ischemia has became a hot spot as stroke can result in symptoms of nerve damages such as hemiplegia, learning and memory disorders. The key factors that cause the death of cells include excitotoxicity, oxidative damage, nitrosative stress and inflammation. However, there is no effective preparation for the treatment of post-ischemic nerve defects at present, so it is urgent to find and develop effective drugs for the treatment of nerve damages after ischemia. Traditional Chinese medicine has advantages and potentials in the treatment of neurological diseases. Many scholars have carried out related researches on the active ingredients of traditional Chinese medicine and achieved some good results. In this context, the researches on the neuroprotective effects of traditional Chinese medicines such as tetramethylpyrazine, butylphthalide and total saponins of Panax notoginseng were reviewed. The author found that the neuroprotective researches of traditional Chinese medicine mostly focused on anti-apoptosis, anti-inflammatory and anti-oxidative stress, but those effects were not sounique to the nervous system. Furthermore, most ingredients of traditional Chinese medicine showed a poor water-soluble property. In view of the research status and existing problems of traditional Chinese medicine in nerve injury, the suggestions for the research and development of the potent neuroprotective agents were proposed in this study from the perspective of pharmacological mechanism research and preparation theory.
Benzofurans/therapeutic use* ; Brain Ischemia/drug therapy* ; Cerebral Infarction/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional ; Neuroprotective Agents/therapeutic use* ; Panax notoginseng ; Pyrazines/therapeutic use* ; Saponins/therapeutic use*

OBJETIVETo investigate the neuroprotective effects and underlying mechanisms of salvianolic acid B (Sal B) extracted from Salvia miltiorrhiza on hippocampal CA1 neurons in mice with cerebral ischemia reperfusion injury.

METHODSForty male National Institute of Health (NIH) mice were randomly divided into 4 groups with 10 animals each, including the sham group, the model group, the SalB group (SalB 22.5 mg/kg) and the nimodipine (Nim) group (Nim 1 mg/kg). A mouse model of cerebral ischemia and reperfusion injury was established by bilateral carotid artery occlusion for 30 min followed by 24-h reperfusion. The malondialdehyde (MDA) content, the nitric oxide synthase (NOS) activity, the superoxide dismutase (SOD) activity and total antioxidant capability (T-AOC) of the pallium were determined by biochemistry methods. The morphologic changes and Bcl-2 and Bax protein expression in hippocampal CA1 neurons were observed by using hematoxylineosin staining and immunohistochemistry staining, respectively.

RESULTSIn the SalB group, the MDA content and the NOS activity of the pallium in cerebral ischemia-reperfusion mice significantly decreased and the SOD activity and the T-AOC significantly increased, as compared with the model group (P<0.05 or P<0.01). The SalB treatment also rescued neuronal loss (P<0.01) in the hippocampal CA1 region, strongly promoted Bcl-2 protein expression (P<0.01) and inhibited Bax protein expression (P<0.05).

CONCLUSIONSSalB increases the level of antioxidant substances and decreases free radicals production. Moreover, it also improves Bcl-2 expression and reduces Bax expression. SalB may exert the neuroprotective effect through mitochondria-dependent pathway on hippocampal CA1 neurons in mice with cerebral ischemia and reperfusion injury and suggested that SalB represents a promising candidate for the prevention and treatment of ischemic cerebrovascular disease.

Animals ; Antioxidants ; pharmacology ; therapeutic use ; Benzofurans ; chemistry ; pharmacology ; therapeutic use ; Brain Ischemia ; complications ; drug therapy ; CA1 Region, Hippocampal ; pathology ; Cell Count ; Immunohistochemistry ; Male ; Malondialdehyde ; metabolism ; Mice ; Neurons ; drug effects ; pathology ; Nitric Oxide Synthase ; metabolism ; Reperfusion Injury ; complications ; drug therapy ; Superoxide Dismutase ; metabolism ; bcl-2-Associated X Protein ; metabolism

BACKGROUNDDl-3-n-butylphthalide (NBP), first isolated from the seeds of celery, showed efficacy in animal models of stroke. This study was a clinical trial to assess the efficacy and safety of NBP with a continuous dose regimen among patients with acute ischemic stroke.

METHODSA randomized, double-blind, double-dummy trial enrolled 573 patients within 48 hours of onset of ischemic stroke in China. Patients were randomly assigned to receive a 14-day infusion of NBP followed by an NBP capsule, a 14-day infusion of NBP followed by aspirin, or a 14-day infusion of ozagrel followed by aspirin. The efficacy measures were Barthel index score and the modified Rankin scale (mRS) at day 90. Differences among the three groups on mRS were compared using χ(2) test of proportions (with two-sided α = 0.05) and Logistic regression analysis was conducted to take the baseline National Institutes of Health Stroke Scale (NIHSS) score into consideration.

RESULTSAmong the 535 subjects included in the efficacy analysis, 90-day treatment with NBP was associated with a significantly favorable outcome than 14-day treatment with ozagrel as measured by mRS (P < 0.001). No significant difference was found among the three groups on Barthel index at day 90. The rate of adverse events was similar among the three groups.

CONCLUSIONSThe 90-day treatment with NBP could improve outcomes at the third month after stroke. The NBP treatment (both intravenous and oral) is safe (ChiCTR-TRC-09000483).

Adult ; Aged ; Benzofurans ; administration & dosage ; therapeutic use ; Double-Blind Method ; Female ; Humans ; Male ; Middle Aged ; Stroke ; drug therapy ; Treatment Outcome

Benzofurans ; therapeutic use ; China ; Fibrinolytic Agents ; therapeutic use ; Humans ; Stroke ; drug therapy

As one of the main water-soluble composites of Radix Salviae, salvianolic acid B is a phenolic acid ingredient of the Chinese drug, which is rich content in the herb and has strong pharmaceutical activity. It is used to treat cardiocerebral vascular diseases, antagonize hepatic/renal fibrosis, prevent cancer, and promote stem cell proliferation and differentiation. In the researches of its acting mechanisms, rather deepened studies have been carried out for its application on cardiocerebral vascular diseases, but that for others are rather fewer.
Benzofurans ; pharmacology ; therapeutic use ; Biomedical Research ; trends ; Disease ; Humans ; Medicine, Chinese Traditional ; trends ; Stem Cells ; drug effects ; Ventricular Remodeling ; drug effects

In this review, the researches on Chinese herb components with anti-hepatic fibrosis activity in China in the recent 20 years were generalized. Almost thirty active herb components attracted author's attention, especially, salvianolic acid B and oxymatrine which were investigated comprehensively. Moreover, the author considered that, in view of the complex pathogenesis and the multi-pathway and multi-target superiority of Chinese medicine formula, the effective components formula investigations deserve more attention and probably prompt a potential researching direction.
Alkaloids ; therapeutic use ; Animals ; Attention ; Benzofurans ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Liver Cirrhosis ; drug therapy ; Quinolizines ; therapeutic use

Benzofurans ; therapeutic use ; Humans ; Neuroprotective Agents ; therapeutic use ; Oxidative Stress ; drug effects

BACKGROUNDAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive death of the upper and lower motor neurons. Transgenic mice over-expressing a mutant form of the human SOD1 gene develop an ALS-like phenotype. Currently, there is no effective treatment or drug for the fatal disease. Previous studies reported potent efficacy of dl-3-n-butylphthalide (DL-NBP) for several neurodegenerative disorders and cerebral ischemia. SOD1-G93A mice are a mouse model of ALS. In this study, we investigated the efficacy of DL-NBP on this ALS mouse model.

METHODSSixty SOD1-G93A female mice were divided into four groups. The vehicle control group received 0 mg×kg(-1)×d(-1) DL-NBP. The experimental groups received DL-NBP with doses of 30, 60 or 120 mg×kg(-1)×d(-1), respectively. For measurement of motor activity, the hanging wire test and rotarod test were performed. Survival statistics were analyzed by Kaplan-Meier survival curves. The body weight of each mouse was recorded twice per week. The statistical motor unit number estimation (MUNE) technique was used to estimate the number of functioning motor units in gastrocnemius muscle. Muscle morphology was evaluated by hematoxylin and eosin staining. Motor neuron quantitation was performed by Nissl staining and microglia activation was observed by immunohistochemistry.

RESULTSOral administration of 60 mg×kg(-1)×d(-1)1 DL-NBP significantly prolonged survival ((164.78 ± 16.67) days) of SOD1-G93A mice compared with vehicle control ((140.00 ± 16.89) days). Treating mice with DL-NBP (60 mg×kg(-1)×d(-1)) significantly decreased the progression rate of motor deficits and suppressed body weight reduction. Furthermore, we found that treating SOD1-G93A mice with DL-NBP (60 mg×kg(-1)×d(-1)) slowed the rate of MUNE reduction (P < 0.01). Motor neurons were remarkably preserved in the anterior horns in mice treated with DL-NBP (60 mg×kg(-1)×d(-1)) at the stage of 19 weeks (P < 0.01). Treating mice with DL-NBP (60 mg×kg(-1)×d(-1)) significantly reduced CD11b immunoreactivity compared with vehicle control mice (P < 0.05). No significant effect was observed in mice treated with DL-NBP of 30 or 120 mg×kg(-1)×d(-1).

CONCLUSIONSThe post-disease-onset administration of DL-NBP significantly prolonged survival and improved motor performance in SOD1-G93A mice. DL-NBP may be a potential therapeutic agent for ALS.

Administration, Oral ; Amyotrophic Lateral Sclerosis ; drug therapy ; Animals ; Benzofurans ; administration & dosage ; therapeutic use ; Disease Models, Animal ; Female ; Immunohistochemistry ; Mice ; Mice, Transgenic