This article is to investigate the effect of piperine on the small intestine of mice with Parkinson's disease with dementia(PDD). Ninety-six C57 BL/6 mice of SPF grade were randomly divided into 8 groups(male, 12 in each group): normal group, model group, autophagy inhibitor group(6-amino-3-methylpurine, 3 MA, 30 mg·kg~(-1)), autophagy activator group(rapamycin, 1 mg·kg~(-1)), low, medium, and high dose piperine groups(10, 20, 40 mg·kg~(-1)), and medopar group(112.5 mg·kg~(-1)). Except for the normal group, mice in each group were injected subcutaneously with reserpine(0.1 mg·kg~(-1)) once every 48 hours for 40 days. In addition, on the 20 th day of administration, except for the normal group, the mice in the other groups were subjected to bilateral common carotid artery occlusion to finally prepare PDD models. At the same time, each group was given the corresponding drug treatment once a day for 40 days. After the last administration, the behavioral changes of mice were observed by autonomic activity experiment and hot plate experiment. The expression levels of α-synuclein(α-syn) and tyrosine hydroxylase(TH) in the small intestine were detected by immunohistochemistry. The expression levels of beclin-1, microtubule-associated protein 1 light chain 3 B(LC3 B) and p62 in the small intestine were detected by immunofluorescence assay. Hematoxylin-eosin staining was used to observe the pathological morphology of small intestine tissues in each group. Enzyme-linked immunosorbent assay was adopted for detection of β-amyloid precursor protein(APP), p-tau, acetylcholine transferase(ChAT), interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in small intestine. Real-time fluorescent quantitative polymerase chain reaction was used to detect the expression of α-syn, TH, beclin-1, microtubule-associated protein 1 light chain 3(LC3), and p62 mRNA and mmu-miR-99 a-5 p in the small intestine. The results of this study showed that, as compared with the model group, the number of activities, the expression levels of ChAT, TH, and p62 were significantly increased in the 3 MA group, the various piperine dose groups, and the medopar group(P<0.05), and their first foot licking time was shortened; APP, p-tau, IL-6, TNF-α, α-syn, beclin-1, LC3 B and mmu-miR-99 a-5 p expression levels were significantly reduced(P<0.05). However, as compared with the model group, the number of activities, ChAT, TH, and p62 expression levels in the rapamycin group were significantly reduced(P<0.05), and the APP, p-tau, IL-6, TNF-α, α-syn, beclin-1, LC3 B and mmu-miR-99 a-5 p expression levels were significantly increased(P<0.05). As compared with the 3 MA group, the number of activities, ChAT, TH, and p62 expression levels were significantly reduced in the low and medium dose piperine groups and rapamycin group(P<0.05); howe-ver, their first foot licking time was significantly prolonged, APP, p-tau, IL-6, TNF-α, α-syn, beclin-1, LC3 B and mmu-miR-99 a-5 p expression levels were increased significantly(P<0.05). As compared with the medopar group, the number of activities, ChAT, TH, and p62 expression levels were significantly reduced in low dose piperine group and rapamycin group(P<0.05), but their first foot licking time was significantly extended, and APP, p-tau, IL-6, TNF-α, α-syn, beclin-1, LC3 B and mmu-miR-99 a-5 p expression levels were significantly increased(P<0.05). In addition, as compared with the normal group, the small intestinal epithelial cells of the model group and the rapamycin group were shed off a lot, with severe damages of intestinal mucosa as well as edema and shedding of the small intestine villi. After administration of the therapeutic interventions, the small intestinal epithelial cells of the 3 MA group, each dose group of piperine, and the medopa group were slightly damaged and the villi were slightly shed off. In summary, piperine has a protective effect on the small intestine of PDD model mice, showing reduced expression of mmu-miR-99 a-5 p, pro-inflammatory factors and autophagy factors, and the mechanism of slowing PDD pathological symptoms may be related to the inhibition of autophagy.
Alkaloids ; Animals ; Autophagy ; Benzodioxoles ; Dementia ; Intestine, Small ; Male ; Mice ; Parkinson Disease ; Piperidines ; Polyunsaturated Alkamides

AIMTo investigate the antidepressant constituents of Piper laetispicum C. DC.

METHODSThe compounds were enriched by column chromatography on silica gel. Structural determination of the pure compounds was based on extensive analyses of modern spectroscopic methods including MS, HR-MS, UV, IR, 1D- and 2D-NMR spectra. The mouse forced swimming test was used for chasing antidepressant activity.

RESULTSThree amides were isolated and identified as N-isobutyl-(3,4-methylendioxyphenyl)-2E, 4E, 9E-undecatrienoamide (I), N-isobutyl-9-phenyl-2E, 4E-nonadienamide (II) and N-isobutyl-7-phenyl-2E, 4E-heptadienamide (III).

CONCLUSIONN-Isobutyl-(3,4-methylendioxyphenyl)-2E, 4E, 9E-undecatrienoamide (I) is a new compound named as laetispicine. N-Isobutyl-9-phenyl-2E, 4E-nonadienamide (II) and N-isobutyl-7-phenyl-2E, 4E-heptadienamide (III) were isolated for the first time as natural substance.

Antidepressive Agents ; chemistry ; isolation & purification ; Benzodioxoles ; chemistry ; isolation & purification ; Molecular Structure ; Piper ; chemistry ; Plant Leaves ; chemistry ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry

OBJECTIVETo research the absorbed character of piperine in Erxiekang plaster, and piperine by transdermal absorption was determined.

METHODThe percutaneous absorption of piperine in vitro at different times was conducted by Franz osmosis and diffusion apparatus as well as high-performance liquid chromatography.

RESULTIt showed that the piperine through skins of mice gradually increased within the experiment time. After 52 h, the penetration of piperine was 78.51%, and remained basically unchanged.

CONCLUSIONThe method is reliable, and can be used for Erxiekang plaster of determination of transdermal absorption.

Alkaloids ; metabolism ; Animals ; Benzodioxoles ; metabolism ; Linear Models ; Male ; Piperidines ; metabolism ; Polyunsaturated Alkamides ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results ; Skin Absorption

Bicyclol is a new generation of anti-hepatitis drug with China's own intellectual property rights. The chemical structure of bicyclol is new and original. Pharmacological research showed that it has high clinical efficacy in treating chronic hepatitis (HBV) patients and lower side effects. Two metabolites of bicyclol have been isolated: M2 (4-hydroxy-4'-methoxy-5, 6, 5', 6'-bis (methylenedioxy)-2-hydroxylmethyl-2'-methoxycarbonyl biphenyl) and M3 (4'-hydroxy-4-methoxy-5, 6, 5', 6'-bis (methyl enedioxy)-2-hydroxylmethyl-2'-methoxycarbonyl biphenyl). To further study the mechanism, safety, and effectiveness of bicyclol, the M2 and M3 have been total synthesized. The synthesis route is as following: the carboxyl and phenolic hydroxyl group of the aromatic bromide had been separately protected by bromobenzyl, coupling through the intermolecular asymmetric Ullmann reaction and then catalyst hydrogenated, borane reducted, two metabolites of bicyclol M2 and M3 were obtained. The structures were determined by IR, 1H NMR, HRMS. Comparison of hepatoprotective activity of bicyclol and the two metabolites on experimental liver injury, the potency of the metabolites were lower than that of bicyclol.
Alanine Transaminase ; blood ; Animals ; Benzodioxoles ; chemical synthesis ; chemistry ; pharmacology ; Biphenyl Compounds ; metabolism ; Carbon Tetrachloride Poisoning ; Chemical and Drug Induced Liver Injury ; blood ; etiology ; Mice

In this paper, Acousto-Optical tomography is modeled by a linear integral equation and an inverse problem involving a diffusion equation in n-spatial dimensions. We make two-step mathematical model. First, we solve a linear integral equation. Assuming the optical energy fluence rate has been recovered from the previous equation, the absorption coefficient micro is then reconstructed by solving an inverse problem. Numerical experiments are presented for the case n=2. The traditional gradient descent method is used for the numerical simulations. The result of the gradient descent method produces the blurring effect. To get rid of the blurring effect, we suggest the total variation regularization for the minimization problem.
Absorption ; Diffusion ; Drug Combinations ; Models, Theoretical ; Piperonyl Butoxide ; Pyrethrins

The objective of the study was to prepare and evaluate the quality of curcumin-piperinedual drug loaded self-microemulsifying drug delivery system(Cur-PIP-SMEDDS). Simplex lattice design was constructed using optimal oil phase, surfactant and co-surfactant concentration as independent variables, and the curcumin and piperine were used as model drugs to optimize Cur-PIP-SMEDDS formulation. In the present study, the drug loadings of curcumin and piperine, mean particle size of Cur-PIP-SMEDDS were made as indicators, and the experiment design, model building and response surface analysis were established using Design Expert 8. 06 software to optimize and verify the composition of SMEDDS formulation. The quality of Cur-PIP-SMEDDS was evaluated by observing the appearance status, transmission electron microscope micrographs and determining particle diameter, electric potential, drug entrapment efficiency and drug loading of it. As a result, the optimal formulation of SMEDDS was CapryoL 90-Cremophor RH40-TranscutoL HP (10:60:30). The appearance of Cur-PIP-SMEDDS remained clarified and transparent, and the microemulsion droplets appeared spherical without aggregation with uniform particle size distribution. The mean size of microemulsion droplet formed from Cur-PIP-SMEDDS was 15.33 nm, the drug loading of SMEDDS for Cur and PIP were 40.90 mg · g(-1) and 0.97 mg · g(-1), respectively, the drug entrapment efficiency were 94.98% and 90.96%, respectively. The results show that Cur-PIP-SMEDDS can increase the solubility and stability of curcumin significantly, in the expectation of enhancing the bioavailability of it. Taken together, these findings can provide the reference to a preferable choice of the Cur formulation and contribute to therapeutic application in clinical research.
Alkaloids ; chemistry ; Benzodioxoles ; chemistry ; Chemistry, Pharmaceutical ; methods ; Curcumin ; chemistry ; Drug Carriers ; chemistry ; Drug Combinations ; Drug Delivery Systems ; Drugs, Chinese Herbal ; chemistry ; Emulsions ; chemistry ; Methylmethacrylates ; chemistry ; Particle Size ; Piperidines ; chemistry ; Polystyrenes ; chemistry ; Polyunsaturated Alkamides ; chemistry

OBJECTIVETo study the chemical constituents from herb of Rhodobryum roseum.

METHODThe compounds were isolated by column chromatography, and identified by IR, NMR data.

RESULT8 compounds were isolated and identified. They are piperine (1), caffeic acid methyl ester (2), uracil glucoside (3), ursolic acid (4), 5alpha, 8alpha-epidioxy-methylcholesta-6, 22-dien-3beta-ol (5), 5alpha, 8alpha-epidioxy-methylcholesta-6,9(11), 22-trien-3beta-ol (6), beta-sitosterol (7), daucosterol (8).

CONCLUSION7 compounds (1-6,8) were isolated from this plant for the first time.

Alkaloids ; chemistry ; isolation & purification ; Benzodioxoles ; Bryophyta ; chemistry ; Caffeic Acids ; chemistry ; isolation & purification ; Piperidines ; chemistry ; isolation & purification ; Plants, Medicinal ; chemistry ; Polyunsaturated Alkamides ; Sitosterols ; chemistry ; isolation & purification ; Triterpenes ; chemistry ; isolation & purification

Alkaloids ; Animals ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; Anticonvulsants ; pharmacology ; Benzodioxoles ; Oils, Volatile ; isolation & purification ; pharmacology ; Piper ; chemistry ; Piper nigrum ; chemistry ; Piperidines ; isolation & purification ; pharmacology ; Plants, Medicinal ; chemistry ; Polyunsaturated Alkamides

It is well known that Rhododendron sclippenbashii contains the toxic material grayanotoxin. So, Koreans do not eat it, but they do eat azalea although it contains grayanotoxin. That is why there have been no reports about Rhododendron sclippenbashii intoxication after ingesting it intentionally, not accidentally. In this case, the patient was admitted to the emergency room with several toxic symptoms after intentionally consuming 50 blossoms of Rhododendron sclippenbashii to get rid of thirst. Treatment with saline infusion and atropine was successful and the outcome was favorable enough in this case to produce a complete cure without any sequelae at discharge. But toxic symptoms were seen for 24 hours, although the symptoms usually fade in 9 hours. Therefore, we should carefully treat and observe, for over 24 hours, the patient who intentionally ingests about 50 blossoms of Rhododendron sclippenbashii.
Adult ; Atropine ; Bradycardia ; Drug Combinations ; Emergencies ; Flowers ; Humans ; Intention ; Piperonyl Butoxide ; Pyrethrins ; Rhododendron ; Thirst

The goal of osmidrosis operation is not only to be free from odor, but also to leave a minimal operation scar. In practice, however, many patients suffer from unfavorable axillary operation scars. Therefore, we herein report various postoperative axillary scars which we experienced. From January 1991 to December 2006, a total of 270 patients(74 men and 196 women) whose axillary osmidrosis had been treated by various methods more than once were included. We observed pre-existing operation scars of recurred patients who wanted revisional operation. Among the total patients, 118 patients had been treated once, 138 patients less than 5 times, and 14 patients more than 5 times. Previous treatment methods included excision in 216 cases, laser in 188 cases, subdermal excision in 63 cases, ultrasonic liposuction in 25 cases, Kobayashi insulated needles in 29 cases, and botulinum toxin injection in 1 case. We observed irregular scar, wide spread scar, hypertrophic scar, postburn scar, depressed scar, and pigmented scar. Pre-existing operation scars were not improved enough by revisional operation. We propose that it is important to select a proper method to effectively get rid of an axillary odor, leaving a minimal operation scar, because axillary area is not optimal for scar revision.
Botulinum Toxins ; Cicatrix ; Cicatrix, Hypertrophic ; Drug Combinations ; Humans ; Lipectomy ; Male ; Needles ; Odors ; Piperonyl Butoxide ; Pyrethrins ; Ultrasonics