Puerarin Attenuates Cycloheximide-Induced Oxidative Damage and Memory-Consolidation Impairment in Rats.

BACKGROUND: Cycloheximide (CXM), an antifungal antibiotic, causes impaired memory consolidation as a side effect partially by disturbing the activities of the central catecholaminergic and cholinergic system. Some reports indicated that puerarin prevented memory impairment in various models in rodents. However, the protective effects of puerarin on the side effects of cycloheximide for memory consolidation impairment have not yet been investigated. METHODS: The protective effects of puerarin on CXM-induced memory-consolidation impairment, and memory impairment produced by central administration of AF64A neurotoxin, were investigated using a passive avoidance task in rats. A combination of transmitter receptor agonists and antagonists was used to explore the effects of puerarin on nervous system function. The activity of antioxidant defense systems and neurotransmitter systems in the prefrontal cortex and hippocampus were assayed. RESULTS: Systemic (25 and 50 mg/kg, i.p.) or central (5 and 10 µg/brain, i.c.v.) administration of puerarin attenuated CXM-induced memory-consolidation impairment produced by 1.5 mg/kg CXM (s.c.) in rats. The improvements produced by 50 mg/kg puerarin were blocked by cholinergic antagonists, a 5-HT2 receptor agonist, and an adrenergic receptor antagonist. Puerarin (only at 50 mg/kg, i.p.) reversed the CXM-induced alterations of the levels of norepinephrine in the prefrontal cortex and the levels of monoamines in the hippocampus. Puerarin also increased antioxidant-defense-system activities in the prefrontal cortex and hippocampus, which had been decreased by CXM. CONCLUSIONS: We suggested that the attenuating effects of puerarin on CXM-induced memory-consolidation impairment may be due to decrease oxidative damage and the normalition of the neurotransmitter function in the prefrontal cortex and hippocampus.

Poria cocos Lanostane Triterpenoids Extract Promotes Collagen and Hyaluronic Acid Production in D-Galactose-Induced Aging Rats.

The global aging population is expanding at an increasingly rapid pace, with approximately one-fourth of the world's population expected to be composed of elderly individuals by 2050. Aging skin is one of the major characteristics expressed in the elderly. The study comprehensively utilizes both cell and animal experiments to confirm the skin anti-aging effects of Poria cocos (P. cocos), which is one of the most important traditional Chinese medicines classified as tonic Chinese medicine, commonly used to treat physical weakness and aging-associated diseases. We demonstrate in this study that P. cocos lanostane triterpenoids extract (Lipucan®) ameliorates aging skin and promotes collagen accumulation and hyaluronic acid production in galactose-induced aging rats. Purified lanostane triterpenoids were initially identified as active components in P. cocos, which significantly increased collagen and hyaluronic acid levels in cultured human skin cells.

Carnosic acid attenuated cytochrome c release through the mitochondrial structural protein Mic60 by PINK1 in SH-SY5Y cells.

Mitochondrial dysfunction has been implicated in Parkinson's disease. Mic60 is a critical component of mitochondrial crista remodeling and participates in maintaining mitochondrial structure and function. This study investigated whether the carnosic acid (CA) of rosemary protects the mitochondria of SH-SY5Y cells against the neurotoxicity of 6-hydroxydopamine (6-OHDA) by regulating Mic60. Our results showed that CA pretreatment reversed the reduction in the Mic60 and citrate synthase proteins, as well as the protein induction of PKA caused by 6-OHDA. Moreover, Mic60 and PINK1 siRNAs blocked the ability of CA to lessen the release of mitochondrial cytochrome c by 6-OHDA. As shown by immunoprecipitation assay, in 6-OHDA-treated cells, the interaction of Mic60 with its phosphorylated threonine residue was decreased, but the interaction with its phosphorylated serine residue was increased. PINK1 siRNA and forskolin, a PKA activator, reversed these interactions. Moreover, forskolin pretreatment prevented CA from rescuing the interaction of PINK1 and Mic60 and the reduction in cytochrome c release and mitophagy impairment in 6-OHDA-treated cells. In conclusion, CA prevents 6-OHDA-induced cytochrome c release by regulating Mic60 phosphorylation by PINK1 through a downregulation of PKA. The regulation of Mic60 by CA can be considered as a protective mechanism for the prevention of Parkinson's disease.

Therapeutic Potential and Mechanisms of Novel Simple O-Substituted Isoflavones against Cerebral Ischemia Reperfusion.

Isoflavones have been widely studied and have attracted extensive attention in fields ranging from chemotaxonomy and plant physiology to human nutrition and medicine. Isoflavones are often divided into three subgroups: simple O-substituted derivatives, prenylated derivatives, and glycosides. Simple O-substituted isoflavones and their glycosides, such as daidzein (daidzin), genistein (genistin), glycitein (glycitin), biochanin A (astroside), and formononetin (ononin), are the most common ingredients in legumes and are considered as phytoestrogens for daily dietary hormone replacement therapy due to their structural similarity to 17-ß-estradiol. On the basis of the known estrogen-like potency, these above isoflavones possess multiple pharmacological activities such as antioxidant, anti-inflammatory, anticancer, anti-angiogenetic, hepatoprotective, antidiabetic, antilipidemic, anti-osteoporotic, and neuroprotective activities. However, there are very few review studies on the protective effects of these novel isoflavones and their related compounds in cerebral ischemia reperfusion. This review primarily focuses on the biosynthesis, metabolism, and neuroprotective mechanism of these aforementioned novel isoflavones in cerebral ischemia reperfusion. From these published works in in vitro and in vivo studies, simple O-substituted isoflavones could serve as promising therapeutic compounds for the prevention and treatment of cerebral ischemia reperfusion via their estrogenic receptor properties and neuron-modulatory, antioxidant, anti-inflammatory, and anti-apoptotic effects. The detailed mechanism of the protective effects of simple O-substituted isoflavones against cerebral ischemia reperfusion might be related to the PI3K/AKT/ERK/mTOR or GSK-3ß pathway, eNOS/Keap1/Nrf-2/HO-1 pathway, TLRs/TIRAP/MyD88/NFκ-B pathway, and Bcl-2-regulated anti-apoptotic pathway. However, clinical trials are needed to verify their potential on cerebral ischemia reperfusion because past studies were conducted with rodents and prophylactic administration.

Carnosic Acid Alleviates Levodopa-Induced Dyskinesia and Cell Death in 6-Hydroxydopamine-lesioned Rats and in SH-SY5Y Cells.

The present study investigated the impact of carnosic acid (CA) from rosemary on the levodopa (L-dopa)-induced dyskinesia (LID) in rats treated with 6-hydroxydopamine (6-OHDA). To establish the model of LID, 6-OHDA-lesioned rats were injected intraperitoneally with 30 mg/kg L-dopa once a day for 36 days. Rats were daily administrated with 3 or 15 mg/kg CA by oral intubation prior to L-dopa injection for 4 days. Rats pretreated with CA had reduced L-dopa-induced abnormal involuntary movements (AIMs) and ALO scores (a sum of axial, limb, and orofacial scores). Moreover, the increases of dopamine D1-receptor, p-DARPP-32, ΔFosB, p-ERK1/2, and p-c-Jun ser63, along with the decrease in p-c-Jun ser73, induced by L-dopa in 6-OHDA-treated rats were significantly reversed by pretreatment with CA. In addition, we used the model of SH-SY5Y cells to further examine the neuroprotective mechanisms of CA on L-dopa-induced cytotoxicity. SH-SY5Y cells were treated with CA for 18 h, and then co-treated with 400 µM L-dopa for the indicated time points. The results showed that pretreatment of CA attenuated the cell death and nuclear condensation induced by L-dopa. By the immunoblots, the reduction of Bcl-2, p-c-Jun ser73, and parkin and the induction of cleaved caspase 3, cleaved Poly (ADP-ribose) polymerase, p-ERK1/2, p-c-Jun ser63, and ubiquitinated protein by L-dopa were improved in cells pretreated with CA. In conclusion, CA ameliorates the development of LID via regulating the D1R signaling and prevents L-dopa-induced apoptotic cell death through modulating the ERK1/2-c-Jun and inducing the parkin. This study suggested that CA can be used to alleviate the adverse effects of LID for PD patients.

Antioxidant Effects and Phytochemical Properties of Seven Taiwanese Cirsium Species Extracts.

In the present investigation, we compared the radical-scavenging activities and phenolic contents of seven Taiwanese Cirsium species with a spectrophotometric method. We further analyzed their phytochemical profiles with high-performance liquid chromatography-photodiode array detection (HPLC-DAD). We found that the flower part of Cirsium japonicum var. australe (CJF) showed the best radical-scavenging activities against 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and the hypochlorite ion, for which the equivalents were 6.44 ± 0.17 mg catechin/g, 54.85 ± 0.66 mmol Trolox/g and 418.69 ± 10.52 mmol Trolox/g respectively. CJF also had the highest contents of total phenolics (5.23 ± 0.20 mg catechin/g) and phenylpropanoids (29.73 ± 0.72 mg verbascoside/g). According to the Pearson's correlation coefficient, there was a positive correlation between the total phenylpropanoid content and ABTS radical-scavenging activities (r = 0.979). The radical-scavenging activities of the phenylpropanoids are closely related to their reducing power (r = 0.986). HPLC chromatograms obtained in validated HPLC conditions confirm that they have different phytochemical profiles by which they can be distinguished. Only CJF contained silicristin (0.66 ± 0.03 mg/g) and silydianin (9.13 ± 0.30 mg/g). CJF contained the highest contents of apigenin (5.56 ± 0.09 mg/g) and diosmetin (2.82 ± 0.10 mg/g). Among the major constituents, silicristin had the best radical-scavenging activities against DPPH (71.68 ± 0.66 mg catechin/g) and ABTS (3.01 ± 0.01 mmol Trolox/g). However, diosmetin had the best reducing power and radical-scavenging activity against the hypochlorite anion (41.57 ± 1.14 mg mmol Trolox/g). Finally, we found that flavonolignans (especial silicristin and silydianin) and diosmetin acted synergistically in scavenging radicals.

Molecular interaction of cytotoxic anticancer analogues as inhibitors of ß-tubulin protein against UACC-62 melanoma cell.

In previous research, a series of cytotoxic anticancer analogues related to 2-acylamino-1,4-naphthoquinone derivatives has been demonstrated. As microtubule plays an important role in many essential cellular processes such as mitosis, tubulin is an important target of anticancer drug. This study performed molecular docking simulation, pharmacophore model, comparative force field analysis model and comparative similarity indices analysis model to investigate the relationship between inhibitory activities and the properties of compounds, in order to further progress the development of cytotoxic anticancer analogues. These compounds have common H-bond interactions with key residues Lys254 and Lys352, but compounds with large R2 substituent have different docking poses than compounds with small R2 substituent. Some of derivatives such as compound 18 formed the H-bonds with residue Lys254 using the oxygen atoms in R1 substituent and formed π-cation interactions with residue Lys352 using phenyl moiety of 1,4-naphthoquinone. The R1 substituent of these compounds preferred to have disfavoured hydrophobic fields and favourable space towards the direction of residue Asn258, while the R2 substituent of these compounds preferred to have about 2-3 carbon chain length hydrophobic substituent towards the direction of residues Ala316 and Lys352. These results offer some beneficial advices for further study in anticancer drug development process.

LED Lights Affecting Morphogenesis and Isosteroidal Alkaloid Contents in Fritillaria cirrhosa D. Don-An Important Chinese Medicinal Herb.

Investigations were carried out to study the effects of light-emitting diode (LED) lights on growth and development of isosteroidal alkaloids in embryogenic calli of Fritillaria cirrhosa D. Don, an important traditional Chinese medicine herb. Calli were cultured in glass bottles, each containing 100 mL of Murashige and Skoog's basal medium supplemented with 2% sucrose and 0.4% gellan gum powder, a gelling agent. These bottles were incubated in a specially designed plant growth chamber equipped with eight different LED lights consisting of single or combinations of four different light spectra emitting blue (450 nm), green (525 nm), red (660 nm), and far-red (730 nm) light. After three months of incubation, morphological changes in embryogenic calli were recorded, and LC-MS/MS analysis of cultures was carried out for peimisine, sipeimine, peiminine, and peimine. The highest number of somatic embryos and the maximum fresh weight was recorded in calli incubated under red (9R), infrared (9IR), and a combination of red+blue+infrared (3R3B3IR), respectively, in decreasing order. The highest contents of peimisine, peiminine, and peimine were recorded under red (9R) and infrared (9IR) lights, respectively. Eight LED lights had significant effects on the morphogenesis of embryogenic calli of F. cirrhosa D. Don and contents of isosteroidal alkaloids.

Steroid-Enriched Fraction of Achyranthes bidentata Protects Amyloid ß Peptide 1-40-Induced Cognitive Dysfunction and Neuroinflammation in Rats.

The roots of Achyranthes bidentata Blume (AB) is commonly used in the treatment of osteoporosis and dementia in traditional Chinese medicine. Pharmacological reports evidenced that AB possessed anti-osteoarthritis effects. However, there is little literature about the anti-dementia activities of AB. The present study was designed to prepare steroid-enriched fraction of AB (ABS) and investigate whether ABS can protect from cognitive dysfunction and neuroinflammation against Aß 1-40-induced Alzheimer's disease (AD) model in rats. ABS only contained 135.11 ± 4.28 mg of ecdysterone per gram. ABS (50 mg/kg) reversed the dysfunction of exploratory activity and memory function on plus-maze and Morris water maze caused by Aß 1-40 in rats. ABS (50 mg/kg) also decreased amyloid deposition, neurofibrillary tangle, neural damage, activated astrocyte, and microglial caused by Aß 1-40. Furthermore, ABS reversed the phenomenon of neural oxidative damage and neuroinflammation, including the higher levels of MDA and cytokines, and the lower activities of antioxidant enzymes and GSH levels caused by Aß 1-40 in rat cortex and hippocampus. Finally, ABS restored the activation of ERK pathway and decreased NF-κB phosphorylation and translocation altered by Aß 1-40. ABS alone (50 mg/kg) promoted cognitive function, activated brain antioxidant defense system, and decreased brain TNF-α levels in sham group. Therefore, ABS has the cognition-promoting and antidementia potential. Steroids especial ecdysterone are major active components of AB. The action mechanism is due to decreasing oxidative stress and neuroinflammation through modulating ERK pathway, NF-κB phosphorylation, and translocation in Aß 1-40-induced AD rat model.

Sophora Tomentosa Extract Prevents MPTP-Induced Parkinsonism in C57BL/6 Mice Via the Inhibition of GSK-3ß Phosphorylation and Oxidative Stress.

Sophora species are used as dietary medicines in aging-associated symptoms. Sophora tomentosa L. (ST) is a native medicinal plant in Southeast Asia; however, there is no pharmacological literature about ST extract. The present study evaluates the antioxidant phytoconstituent contents and radical scavenging capacities of ST extract. The further investigation was to clarify the neuroprotective mechanism of ST extract against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism by assaying the activities of the dopaminergic system and antioxidant defenses, glycogen synthase kinase 3ß (GSK3-ß) phosphorylation, and α-synuclein levels in C57BL/6 mice. The results show that ST extract alleviated the motor deficits in MPTP-induced Parkinsonism with four behavioral tests, including a rearing locomotor, catalepsy test, balance beam walking test, and pole test. ST extract reversed the number of tyrosine hydroxylase (TH)-positive neurons in substantia nigra (SN) that had decreased by MPTP. ST extract also restored the decreased levels of dopamine and the expression of tyrosine hydroxylase (TH) in the striatum. Furthermore, ST extract restored the levels of glutathione (GSH) and the activities of antioxidant enzymes, and decreased the elevated levels of malondialdehyde (MDA) in mouse striatum. ST extract also decreased α-synuclein overexpression and GSK-3ß phosphorylation in mouse striatum. In vitro, ST extract exerted higher 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical scavenging capacities through its higher phenolic contents, especially protocatechuic acid and epicatechin. These results suggest that ST extract has the potential to counteract MPTP-induced motor deficit. The neuroprotective mechanism of ST extract against MPTP-induced Parkinsonism might be related to decreasing GSK-3ß phosphorylation and restoring the activities of striatal antioxidant defenses to restore the nigrostriatal dopaminergic function and decrease α-synuclein accumulation.

Differential change in cortical and hippocampal monoamines, and behavioral patterns in streptozotocin-induced type 1 diabetic rats.

OBJECTIVES: Diabetes mellitus (DM) is a widespread metabolic disorder worldwide. Clinical physicians have found diabetic patients have mild to middle cognitive dysfunction and an alteration of brain monoaminergic function. This study explored the change in various patterns of behavioral models and brain monoamine function under streptozotocin (STZ)-induced type 1 diabetes. MATERIALS AND METHODS: We established a type 1 DM model via intravenous injection with STZ (65 mg/kg) in rats. Three weeks after the STZ injection, various behavioral measurements including the inhibitory avoidance test, active avoidance test and Morris water maze were conducted. Finally, all rats were dissected and the concentrations of monoamines and their metabolites in cortex and hippocampus were measured by high performance liquid chromatography with electrochemical detection. RESULTS: We found that STZ induced type 1 diabetes (hyperglycemia and lack of insulin) in rats. STZ-induced diabetic rats had cognitive impairment in acquisition sessions and long-term retention of the active avoidance test. STZ-induced diabetic rats also had cognitive impairment in spatial learning, reference and working memory of the Morris water maze. STZ significantly reduced concentrations of norepinephrine (NE) in the cortex and dopamine (DA) in the hippocampus, but increased concentrations of DA and serotonin (5-HT) in the cortex 35 days after injection. The concentration of 5-HT in the hippocampus was also significantly increased. CONCLUSION: The data suggested that this cognitive impairment after a short-term period of STZ injection might be related to cortical NE dysfunction, differential alteration of cortical and hippocampal DA function, and brain 5-HT hyperfunction.

Cuscuta chinensis and C. campestris Attenuate Scopolamine-Induced Memory Deficit and Oxidative Damage in Mice.

The seeds of Cuscuta chinensis Lam. and C. campestris Yuncker have been commonly used as Chinese medical material for preventing aging. Our previous studies have found that C. chinensis and C. campestris possess anti-inflammatory activities in rodents. However, their other biological activities, such as memory-improving properties, have not yet been explored. In the present study, we examined the memory-improving effects of the extracts of C. chinensis and C. campestris on scopolamine (SCOP)-induced memory deficit and explored their underlying mechanism in mice. Both Cuscuta species improved SCOP-induced memory deficits in the passive avoidance test, elevated plus-maze, and spatial performance test of the Morris water maze in mice. In addition, compared with mice injected with SCOP, mice pretreated with both Cuscuta species stayed for a longer time on the platform for the probe test of the Morris water maze. Moreover, both Cuscuta species reduced brain acetylcholinesterase activity and malondialdehyde levels that were increased by SCOP, and the species restored the activities of antioxidant enzymes (superoxide dismutase and catalase) and the levels of glutathione that were decreased by SCOP in the brains of mice. Both Cuscuta species further decreased brain interleukin-1ß and tumor necrosis factor-α levels that were elevated by SCOP. We demonstrated that both Cuscuta species exhibited a protective activity against SCOP-induced memory deficit, cholinergic dysfunction, oxidative damage, and neuroinflammation in mice, and C. campestris has better potential than C. chinensis. In addition, we provided evidence that the seeds of C. campestris can be used as Cuscutae Semen in Traditional Chinese Medicine.

Aqueous Extract of Davallia mariesii Attenuates 6-Hydroxydopamine-Induced Oxidative Damage and Apoptosis in B35 Cells Through Inhibition of Caspase Cascade and Activation of PI3K/AKT/GSK-3ß Pathway.

The medicinal ferns of Polydiaceae and Davalliaceae species are called "Gusuibu" by Chinese physicians and used as antiaging dietary medicines. Our previous report revealed that Drynaria fortunei (Polydiaceae) protected against 6-hydroxydopamine (6-OHDA)-induced oxidative damage via the PI3K/AKT pathway in B35 neuroblastoma cells. The present study compares the antioxidant phytoconstituent contents and radical scavenging capacities of five Davalliaceae species. The further aim was to clarify the protective mechanism of Davallia mariesii (DM) against 6-OHDA-induced oxidative damage and apoptosis in B35 cells. The results show that Araiostegia perdurans (AP) and DM extracts have better radical scavenging capacities against 1,1-diphenyl-2-picryhydrazyl (DPPH) and reactive oxygen species (ROS) than other Davalliaceae species. However, only DM extract inhibited 6-OHDA autoxidation under cell-free systems and increased cell viability, compared to B35 cells solely exposed to 6-OHDA. DM extract decreased apoptosis and restored mitochondrial expression in 6-OHDA-treated B35 cells. Additional data indicated that DM extract decreased intracellular ROS and nitric oxide levels generated by 6-OHDA exposure. DM extract also restored glutathione (GSH) levels and the activities of glutathione peroxidase and reductase, and then decreased the elevated malondialdehyde (MDA) levels. Finally, DM extract regulated the protein expression of the caspase cascade and PI3K/AKT/GSK-3ß pathways. These results suggest that the protective mechanism of DM extract against 6-OHDA-induced oxidative damage and apoptosis might be related to its radical scavenging capacity, maintaining the mitochondrial function to inhibit the Bcl-2/caspase cascade pathway and activating intracellular antioxidant defenses (GSH recycling, HO-1 and NQO-1) by modulating the activation of the PI3K/AKT/GSK-3ß pathway.

Comparison of the Hepatoprotective Effects of Four Endemic Cirsium Species Extracts from Taiwan on CCl4-Induced Acute Liver Damage in C57BL/6 Mice.

Species of Cirsium (Asteraceae family) have been used in folk hepatoprotective medicine in Taiwan. We collected four Cirsium species—including the aerial part of Cirsium arisanense (CAH), the aerial part of Cirsium kawakamii (CKH), the flower part of Cirsium japonicum DC. var. australe (CJF), and Cirsii Herba (CH)—and then made extractions from them with 70% methanol. We compared the antioxidant contents and activities of these four Cirsium species extracts by a spectrophotometric method and high-performance liquid chromatography⁻photodiode array detector (HPLC-DAD). We further evaluated the hepatoprotective effects of these extracts on CCl4-induced acute liver damage in C57BL/6 mice. The present study found CAH possesses the highest antioxidant activity among the four Cirsium species, and these antioxidant activities are closely related to phenylpropanoid glycoside (PPG) contents. The extracts decreased serum ALT and AST levels elevated by injection with 0.2% CCl4. However, only CJF and CH decreased hepatic necrosis. Silibinin decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and hepatic necrosis caused by CCl4. CJF and CH restored the activities of hepatic antioxidant enzymes and decreased hepatic malondialdehyde (MDA) levels. CJF further restored the expression of hepatic antioxidant enzymes including Cu/Zn-superoxide dismutase (Cu/Zn-SOD), Mn-superoxide dismutase (Mn-SOD), and glutathione S-transferase (GST) proteins. HPLC chromatogram indicated that CKH, CJF, and CH contained silibinin diastereomers (α and β). Only CJF contained diosmetin. Hence, the hepatoprotective mechanism of CJF against CCl4-induced acute liver damage might be involved in restoring the activities and protein expression of the hepatic antioxidant defense system and inhibiting hepatic inflammation, and these hepatoprotective effects are related to the contents of silibinin diastereomers and diosmetin.

Antihemolytic and antioxidant properties of pearl powder against 2,2'-azobis(2-amidinopropane) dihydrochloride-induced hemolysis and oxidative damage to erythrocyte membrane lipids and proteins.

Pearl powder, a well-known traditional mineral medicine, is reported to be used for well-being and to treat several diseases from centuries in Taiwan and China. We investigated the in vitro antihemolytic and antioxidant properties of pearl powder that could protect erythrocytes against 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced oxidative damage to membrane proteins/lipids. Human erythrocytes were incubated with different concentrations of pearl powder (50-200 µg/mL) for 30 minutes and then exposed to AAPH for 2-6 hours. We found that AAPH alone time dependently increased the oxidative hemolysis of erythrocytes, while pearl powder pretreatment substantially inhibited the hemolysis in a concentration-/time-dependent manner. AAPH-induced oxidative damage to erythrocyte membrane lipids was evidenced by the elevated malondialdehyde (MDA) levels. However, pearl powder remarkably inhibited the malondialdehyde formation, and the 200 µg/mL concentration showed almost similar malondialdehyde values to the control. Furthermore, pearl powder suppressed the AAPH-induced high-molecular-weight protein formation and concomitantly increased the low-molecular-weight proteins in erythrocytes. Antioxidant potential that was measured as superoxide dismutase activity and glutathione content was significantly dropped by AAPH incubation, which suggests the vulnerability of erythrocytes to AAPH-induced oxidative stress. Noteworthy, erythrocytes pretreated with pearl powder showed restored superoxide dismutase activity and glutathione levels against AAPH-induced loss. Our findings conclude that pearl powder attenuate free radical-induced hemolysis and oxidative damage to erythrocyte membrane lipids/proteins. The potent antioxidant property of pearl powder may offer protection from free radical-related diseases.

Echinacoside ameliorates the memory impairment and cholinergic deficit induced by amyloid beta peptides via the inhibition of amyloid deposition and toxicology.

Echinacoside is a phenylethanoid glycoside and possesses neuroprotective activity in vitro and in vivo. This study investigates the role of the amyloid cascade and central neuronal function on the protective effects of echinacoside in amyloid ß peptide 1-42 (Aß 1-42)-treated SH-SY5Y cells and an Aß 1-42-infused rat. Echinacoside inhibited Aß 1-42 oligomerization in vitro and restored the cell viability that was reduced by Aß 1-42 in SH-SY5Y cells. Intracisternal infusion with Aß 1-42 by an osmotic pump caused cognitive deficits, an increase in amyloid deposition and acetylcholinesterase activities, and a decrease in the brain's levels of acetylcholine and dopamine. Echinacoside reduced the cognitive deficits and amyloid deposition, and it reversed the cortical cholinergic dysfunction that was caused by Aß 1-42 in rats. Echinacoside further reversed the memory impairment in the Morris water maze task caused by scopolamine in mice. Therefore, we suggest that echinacoside ameliorated cognitive dysfunction that was caused by Aß 1-42 by blocking amyloid deposition via inhibiting amyloid oligomerization and reversing the cortical cholinergic neuronal function via decreasing amyloid neurotoxicity.

Acteoside and Isoacteoside Protect Amyloid ß Peptide Induced Cytotoxicity, Cognitive Deficit and Neurochemical Disturbances In Vitro and In Vivo.

Acteoside and isoacteoside, two phenylethanoid glycosides, coexist in some plants. This study investigates the memory-improving and cytoprotective effects of acteoside and isoacteoside in amyloid ß peptide 1-42 (Aß 1-42)-infused rats and Aß 1-42-treated SH-SY5Y cells. It further elucidates the role of amyloid cascade and central neuronal function in these effects. Acteoside and isoacteoside ameliorated cognitive deficits, decreased amyloid deposition, and reversed central cholinergic dysfunction that were caused by Aß 1-42 in rats. Acteoside and isoacteoside further decreased extracellular Aß 1-40 production and restored the cell viability that was decreased by Aß 1-42 in SH-SY5Y cells. Acteoside and isoacteoside also promoted Aß 1-40 degradation and inhibited Aß 1-42 oligomerization in vitro. However, the memory-improving and cytoprotective effects of isoacteoside exceeded those of acteoside. Isoacteoside promoted exploratory behavior and restored cortical and hippocampal dopamine levels, but acteoside did not. We suggest that acteoside and isoacteoside ameliorated the cognitive dysfunction that was caused by Aß 1-42 by blocking amyloid deposition via preventing amyloid oligomerization, and reversing central neuronal function via counteracting amyloid cytotoxicity.

Inhibition of JNK by pi class of glutathione S-transferase through PKA/CREB pathway is associated with carnosic acid protection against 6-hydroxydopamine-induced apoptosis.

Pi class of glutathione S-transferase (GST) is known to suppress c-Jun N-terminal kinase (JNK)-related apoptosis through protein-protein interactions. Moreover, signaling by PKA/cAMP response element binding protein (CREB) is necessary for GSTP up-regulation. This study explored whether carnosic acid (CA) from rosemary prevents 6-hydroxydopamine (6-OHDA)-induced neurotoxicity by inhibition of JNK through GSTP via PKA/CREB signaling. Results indicated that the GSTP protein was increased in SH-SY5Y cells treated with CA for 18 and 24 h. However, CA had no significant effect on alpha or mu class of GST. Treatment of CA increased the induction of p-PKAα, nuclear p-CREB, and CRE-DNA binding activity. These effects of CA were attenuated in cells pretreated with the PKA inhibitor H89. CA pretreatment suppressed 6-OHDA-induced apoptosis by inhibition of JNK phosphorylation, poly(ADP)-ribose polymerase cleavage, and nuclear condensation. Pretreatment with H89 and GSTP siRNA attenuated the ability of CA to reverse 6-OHDA-induced apoptosis. By use of immunoprecipitation with JNK antibody to examine the interaction of GSTP-JNK with CA, we showed that CA pretreatment increased the immunoprecipitation of GSTP after 6-OHDA treatment, which suggests that CA promoted the interaction between GSTP and JNK. CONCLUSION: CA prevents 6-OHDA-induced apoptosis via inhibition of JNK by GSTP through the PKA/CREB pathway.

Antitussive, anti-pyretic and toxicological evaluation of Ma-Xing-Gan-Shi-Tang in rodents.

BACKGROUND: Ma-Xing-Gan-Shi-Tang (abbreviated as MXGST), an important Chinese herbal prescribed for cough, bronchial inflammation and fever from pneumonia, consists of four medicinal herbs, including Ephedrae herb, Semen Pruni Armeniacae, licorice and Gypsum. These components, especially Ephedrae and Semen Pruni Armeniacae, possess antitussive activities, but they have severe adverse effects. METHODS: The pharmacological activities of MXGST extract in clinical use were investigated with citric acid-induced cough, acetylcholine/histamine-induced bronchial contraction and lipopolysaccharide (LPS)-induced fever in rodents. The subacute toxicology of MXGST extract was evaluated after a 28-day repeated oral administration in rats. RESULTS: Each gram of MXGST extract contained 60 ± 8 µg of ephedrine, 480 ± 40 µg of glycyrrhizic acid and 440 ± 8 µg of amygdalin according to high performance liquid chromatography and a photodiode array detector. MXGST extract produced pronounced, dose-dependent antitussive effects in guinea pigs and reduced hyperthermic syndrome induced by LPS in rats. MXGST extract blocked the bronchial contraction induced by acetylcholine/histamine. Oral administration of MXGST extract for 28 days did not cause any hematological, biochemical or histological changes in rats. CONCLUSIONS: MXGST extract is a safer, more effective Chinese prescription with antitussive and anti-pyretic effects. The antitussive mechanism of MXGST is related to partially relaxing the bronchial smooth muscle by blocking acetylcholinergic and histaminergic receptors.

Lupeol and Its Role in Chronic Diseases.

Lupeol belongs to pentacyclic lupane-type triterpenes and exhibits in edible vegetables, fruits and many plants. Many researches indicated that lupeol possesses many beneficial pharmacological activities including antioxidant, anti-inflammatory, anti-hyperglycemic, anti-dyslipidemic and anti-mutagenic effects. From various disease-targeted animal models, these reports indicated that lupeol has anti-diabetic, anti-asthma, anti-arthritic, cardioprotective, hepatoprotective, nephroprotective, neuroprotective and anticancer efficiency under various routes of administration such as topical, oral, subcutaneous, intraperitoneal and intravenous. It is worth mentioning that clinical trials of lupeol were performed to treat canine oral malignant melanoma and human moderate skin acne in Japan and Korea. The detailed mechanism of anti-inflammatory, anti-diabetic, hepatoprotective and anticancer activities was further reviewed from published papers. These evidence indicate that lupeol is a multi-target agent to exert diverse pharmacological potency with many potential targeting proteins such as α-glucosidase, α-amylase, protein tyrosine phosphatase 1B (PTP 1B) and TCA cycle enzymes and targeting pathway such as IL-1 receptor-associated kinase-mediated toll-like receptor 4 (IRAK-TLR4), Bcl-2 family, nuclear factor kappa B (NF-kB), phosphatidylinositol-3-kinase (PI3-K)/Akt and Wnt/ß-catenin signaling pathways. This review also provides suggestion that lupeol might be a valuable and potential lead compound to develop as anti-inflammatory, anti-diabetic, hepatoprotective and anticancer drugs.