Piyanuch Rojsanga - Academia.edu (original) (raw)
Papers by Piyanuch Rojsanga
Cancer Letters, 2007
Berberine is known to possess a wide variety of pharmacological activities, including pro-apoptot... more Berberine is known to possess a wide variety of pharmacological activities, including pro-apoptotic activity. However, its molecular targets are not elucidated at present. NAG-1 and ATF3 are induced by several dietary compounds associated with pro-apoptotic activity. Berberine induces cell growth arrest, apoptosis, NAG-1, and ATF3 in human colorectal cancer cells. ATF3 induction by berberine is mediated in a p53-dependent manner, whereas NAG-1 induction by berberine is mediated by multiple signaling pathways. Our results suggest that berberine facilitates apoptosis and that NAG-1 and ATF3 expression plays an important role in berberine-induced apoptosis.
Coscinium fenestratum (Gaertn.) Colebr. (Menispermaceae), called "Hamm" in Thai, is a traditional... more Coscinium fenestratum (Gaertn.) Colebr. (Menispermaceae), called "Hamm" in Thai, is a traditional medicine of the northeastern part of Thailand which is recently very popularly used. Its stem is claimed to be effective against several symptoms. The major components in the stem of this plant are isoquinoline alkaloids such as berberine, palmatine, tetrahydropalmatine, crebanine and jatrorrhizine. At present, berberine content in C. fenestratum has not been reported elsewhere. In the present study berberine content in the stem of this plant was examined. Ten samples of the dried stems were purchased from ten different traditional drugstores from various parts of the country. Extracts of these samples were prepared by maceration with 80% ethanol and the berberine content of each sample was determined by TLCdensitometry. Yields of the crude extracts were in the range of 9.87-16.38% dry weight while berberine contents in the dried powder and in the crude extract were in the ranges of 1.71-2.89% w/w and 11.84-18.45% dry weight, respectively. Thin layer chromatographic fingerprints of each extract showed similar pattern with bands of berberine as the major alkaloid and other minor alkaloids. ©All right reserved.
Evidence-Based Complementary and Alternative Medicine, 2015
The in vitro antioxidant and antibacterial assays against clinically isolated Streptococcus suis ... more The in vitro antioxidant and antibacterial assays against clinically isolated Streptococcus suis and Staphylococcus intermedius of the extracts prepared by decoction and ethanolic reflux of different parts of Chettaphangki (Cladogynos orientalis Zipp. ex Span), including the leaves, roots, and stems, using 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging assay and disc diffusion method were conducted. Quantitative analysis of total phenolic and total flavonoid contents in the extracts using spectrophotometric methods was also performed. Finally, phytochemical screening by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC) was conducted. Leaf ethanolic reflux extract (100 g) contained the highest total phenolic and total flavonoid contents of 7.21 ± 0.28 μg gallic acid equivalent (GAE) and 11.51 ± 2.02 μg rutin equivalent (RE), respectively. Chettaphangki extracts promoted low antioxidant activity with EC50 values in the range of 0.27-0.48 mg/mL. Extracts and fractions from the roots and stems of this plant promoted low to intermediate antibacterial activity against S. intermedius with the inhibition zones between 7 and 14 mm. The chromatographic data suggested that the leaf extracts of C. orientalis contained rutin while the root and stem extracts contained scopoletin and chettaphanin I. Rutin promoted strong antioxidant activity while chettaphanin I showed low antibacterial activity against Staphylococcus intermedius.
Experimental and therapeutic medicine, 2010
Coscinium fenestratum (Gaertn.) Colebr. is traditionally used for the treatment of cancer, arthri... more Coscinium fenestratum (Gaertn.) Colebr. is traditionally used for the treatment of cancer, arthritis and diabetes mellitus. The purpose of this study was to determine the molecular mechanisms by which this plant shows beneficial effects. An 80% ethanolic extract of C. fenestratum (80ET) was separated by its polarity into dichloromethane (DCM) and aqueous fractions (WF), and the anti-proliferative effects of 80ET, DCM and WF were investigated. Berberine, one of the major components of C. fenestratum, was used as a control. The 80ET, DCM, WF and berberine showed anti-proliferative activity as assessed by cell growth assay. Subsequently, the pro-apoptotic proteins NAG-1 and ATF3 were increased and the cell cycle protein cyclin D1 was decreased by the extract and its fractions. Interestingly, only the DCM fraction exhibited the induction of peroxisome proliferator-activated receptor γ (PPARγ) binding activity, which represents a pro-apoptotic activity in colorectal cancer cells. The ove...
Pharmaceutical Biology, 2015
Abstract Context: Thunbergia laurifolia Lindl. (Acanthaceae) is a Thai medicinal plant used for t... more Abstract Context: Thunbergia laurifolia Lindl. (Acanthaceae) is a Thai medicinal plant used for the detoxification of poison which is likely to be beneficial for the treatment of cognitive deficits including Alzheimer's disease. Objective: To elucidate the effects of Thunbergia laurifolia leaf extract (TLL) on cognitive dysfunction and depression-like behavior in olfactory bulbectomized mice (OBX). Materials and methods: OBX mice were treated daily with TLL at the dose of 250 and 500 mg/kg, tacrine, and imipramine, on the day after 10 d of OBX operation. The effects of TLL on cognitive and depression-like behavior of the animals were analyzed. After completing behavioral experiments, the expression levels of cholinergic marker genes encoding ChAT and muscarinic M1 receptor were quantitatively analyzed. Results: TLL and tacrine reduced OBX-induced cognitive deficits in the object recognition test (ORT) with the time spent for the novel object two times longer than that of the familiar object. Moreover, TLL at the dose of 500 mg/kg and imipramine ameliorated depression-like behavior in the tail suspension test (TST) by reducing the duration of immobility from 25.18% to 3.16% and from 25.18% to 6.48%, respectively. TLL at the dose of 250 and 500 mg/kg reversed the OBX-induced down-regulation of ChAT mRNA expression in the hippocampus from 0.12 to 0.17 and 0.24, respectively, while the down-regulation of mRNA expression of muscarinic M1 receptor was also reversed by TLL from 0.23 to 0.38 and 0.48, respectively. Conclusions: TLL ameliorates non-spatial short-term memory deficits in OBX mice, and has the potential to exhibit an antidepressant-like action.
Planta Medica, 2014
ABSTRACT Thai traditional anti-diabetic herbal formula, Mathura Meha, composed of 26 Thai medicin... more ABSTRACT Thai traditional anti-diabetic herbal formula, Mathura Meha, composed of 26 Thai medicinal plants, has been used as alternative and complementary medicine for diabetes treatment in Wang-nam-yen hospital, a model hospital of Thai traditional medicine established by Ministry of Public Health. It is interesting that the formula could control blood glucose level of patients who didn’t respond to conventional hypoglycemic drugs or insulin injection. To provide scientific evidences of efficacy and safety of this herbal formula, in vivo anti-diabetic activity and acute toxicity were investigated. The herbal formula was extracted by 3 different methods, percolation with 80% and 50% ethanol, and water decoction. Single dose oral administration experiments [1] revealed that among 3 extracts, aqueous extract was the most effective extract. It significantly decreased plasma glucose level of streptozotocin-nicotinamide induced diabetic rats [2] at a dose of 50 mg/kg during oral glucose tolerant test (OGTT). Daily oral administration of 25 and 50 mg/kg aqueous extract for 2 weeks [1] significantly lowered 2 hours postprandial plasma glucose level (2h-PPG) of diabetic rats for 8.97% and 11.51%, respectively. There were no sign or symptom of toxicity observed after oral administration of aqueous extract (5 g/kg) [1] to male and female rats for 24 hours and no mortality was observed up to 14 days of monitoring.
Medical Principles and Practice, 2006
To develop the optimal extraction procedure (i.e. maceration, percolation or Soxhlet extraction) ... more To develop the optimal extraction procedure (i.e. maceration, percolation or Soxhlet extraction) and thin- layer chromatographic (TLC)-densitometric method for the determination of berberine content of Coscinium fenestratum. Maceration, percolation and Soxhlet extraction techniques were used to extract alkaloids from dried stems of C. fenestratum. The solvents used were 50 and 80% ethanol. Crude extracts and berberine content recovered from the TLC fingerprint were evaluated for chemical components of each extraction method. Precoated silica gel GF(254) plates were used as stationary phase while butanol:glacial acetic acid:water (14:3:4) was used as a mobile phase. Detection and quantitation of berberine were performed by densitometry at the wavelength of 415 nm over the linearity range of 240-840 ng (r(2) = 0.9982). The relative standard deviations from intraday and interday precisions were less than 4.13%. The recovery of standard berberine was 97.58-98.71% (%RSD = 3.85), and the limit of detection and quantitation were 25 and 50 ng/spot, respectively. Eighty percent ethanol gave a higher content of berberine than 50% ethanol. Berberine contents from maceration, percolation and Soxhlet extraction with 80% ethanol were 3.37+/- 0.30, 3.08+/- 0.38 and 2.67+/- 0.27% w/w, respectively. The TLC-densitometric method was simple, accurate and precise for quantitating berberine in the stem extract of C. fenestratum. Maceration with 80% ethanol gave the highest content of berberine in the extract. TLC of the extracts from different methods showed a similar pattern.
Life Sciences, 2012
The aims of the present study were to investigate the effect of crebanine on memory and cognition... more The aims of the present study were to investigate the effect of crebanine on memory and cognition impairment in mice and to elucidate the underlying molecular mechanisms. The memory-enhancing effects of crebanine were assessed with a water maze test using scopolamine-induced amnesic mice. The molecular mechanism was explored in silico by docking crebanine against acetylcholine binding proteins (AChBPs) and in vitro with a radioligand competition assay using (±)-[(3)H]-epibatidine. The pharmacological behavior was assessed by observing changes to the functional activity of α7-nAChRs expressed in Xenopus oocytes and by fluorescent assays on recombinant ligand gated ion channel (LGIC) receptors expressed in mammalian cells. The administration of crebanine significantly improved the cognitive deficits induced by scopolamine, as measured by the water maze test. The docking results demonstrated that crebanine bound to the active binding site of the AChBP template with a good docking energy. Crebanine significantly inhibited the binding of (±)-[(3)H]-epibatidine to AChBPs with K(i) values of 179 nM and 538 nM for Ls and Ac, respectively. Further functional assays performed using two separate protocols indicated that crebanine is an antagonist of the α7-nAChR with an IC(50) of 19.1μM. The observed actions of crebanine against amnesia and its effect on α7-nAChRs will be beneficial for target-based drug design; crebanine or its scaffold can be used as the starting point to develop a drug for Alzheimer's disease. The cognition-enhancing effects of crebanine and the underlying mechanism based on α7-nAChRs are consistent with its traditional use. These findings demonstrate the potential utility of crebanine in the development of neurodegenerative therapy.
Journal of Biomolecular Screening, 2012
The nicotinic acetylcholine receptors (nAChRs) are a member of the ligand-gated ion channel famil... more The nicotinic acetylcholine receptors (nAChRs) are a member of the ligand-gated ion channel family and play a key role in the transfer of information across neurological networks. The X-ray crystal structure of agonist-bound α 7 acetylcholine binding protein (AChBP) has been recognized as the most appropriate template to model the ligand-binding domain of nAChR for studying the molecular mechanism of the receptor-ligand interactions. Virtual screening of the National Cancer Institute diversity set, a library of 1990 compounds with nonredundant pharmacophore profiles, using AutoDock against AChBPs revealed 51 potential candidates. In vitro radioligand competition assays using [ 3 H] epibatidine against the AChBPs from the freshwater snails, Lymnaea stagnalis, and from the marine species, Aplysia californica and the mutant (AcY55W), revealed seven compounds from the list of candidates that had micromolar to nanomolar affinities for the AChBPs. Further investigation on α 7 nAChR expressing in Xenopus oocytes and on the recombinant receptors with fluorescence resonance energy transfer (FRET)-based calcium sensor expressing in HEK cells showed that seven compounds were antagonists of α 7 nAChR, only one compound (NSC34352) demonstrated partial agonistic effect at low dose (10 µM), and two compounds (NSC36369 and NSC34352) were selective antagonists on α 7 nAchR with moderate potency. These hits serve as novel templates/scaffolds for development of more potent and specific in the AChR systems.
Evidence-Based Complementary and Alternative Medicine, 2013
Acanthopanax trifoliatus is a plant that has been traditionally used in Thailand as a vegetable a... more Acanthopanax trifoliatus is a plant that has been traditionally used in Thailand as a vegetable and a tonic. This study investigated effects of the aqueous extract of its leaves (ATL) on cognitive and emotional deficits using an olfactory bulbectomized mouse (OBX) model. OBX mice were treated daily with ATL (250 and 500 mg/kg, p.o.) 3 days after OBX. Antidementia drug tacrine (2.5 mg/kg/day) and antidepressant drug imipramine (10 mg/kg/day) were given i.p. as reference drugs. OBX significantly impaired cognitive behavior in a novel object recognition test and a modified Y-maze test and induced depression-like behavior in a tail suspension test. ATL and tacrine treatment attenuated OBX-induced cognitive deficits, whereas ATL and imipramine improved OBX-induced depression-like behavior. Neurochemical studies conducted after completing behavioral experiments demonstrated that OBX downregulated the expression levels of cholinergic marker genes encoding choline acetyltransferase and muscarinic M 1 receptor in a manner reversed by ATL and tacrine. Moreover, ATL and tacrine administration inhibited the ex vivo activity of acetylcholinesterase in the brain. These findings suggest that ATL is beneficial for the treatment of cognitive and emotional deficits related to dementia with depressive symptoms and that the antidementia effect of ATL is mediated by normalizing the function of central cholinergic systems.
Carbohydrate Polymers, 2009
The objective of this study was to examine the effects of different storage conditions of star fr... more The objective of this study was to examine the effects of different storage conditions of star fruit (Averrhoa carambola) juice on the activity of acetylcholinesterase in various organs of Sprague Dawley (SD) rats. The effect of oral administration of star fruit on serum lipid profiles was also examined in this study. A total of 15 female rats were assigned into three groups with five animals per group (n=5). The first group served as control group and given only distilled water (vehicle) while the other two groups were given different star fruit preparations, i.e. freshly prepared star fruit juice and after 3 hours storage, respectively. From the results obtained, a significant decrease in the hepatic acetylcholinesterase activity was observed in rats treated with star fruit juice. In conclusion, the star fruit juice at different storage conditions is selectively targeted on the acetylcholinesterase activity in rat liver but not in kidney and heart.
Therapeutic effects of herbal medicine depend on bioactive compounds contained in herbal preparat... more Therapeutic effects of herbal medicine depend on bioactive compounds contained in herbal preparation. The different plant species usually contain different constituents even though they are closely related species which influence their therapeutic effects. Therefore, it is important to ensure that the correct plant species will be used. Thai traditional anti-diabetic herbal formula, Mathura Meha, composed of 26 Thai medicinal plants, has been used as complementary medicine for diabetes treatment in Wang-nam-yen hospital. There were 6 problematic plants that could cause confusing in dried materials verification. Three categories of problems were substitution, confusing between vernacular and scientific names, and closely related species. To confront with these problems, the system for identification of dried material should be set up. In this study, 6 plants were each identified by comparing their microscopical characteristic and TLC chromatograms with authentic sample of all expecte...
Cancer Letters, 2007
Berberine is known to possess a wide variety of pharmacological activities, including pro-apoptot... more Berberine is known to possess a wide variety of pharmacological activities, including pro-apoptotic activity. However, its molecular targets are not elucidated at present. NAG-1 and ATF3 are induced by several dietary compounds associated with pro-apoptotic activity. Berberine induces cell growth arrest, apoptosis, NAG-1, and ATF3 in human colorectal cancer cells. ATF3 induction by berberine is mediated in a p53-dependent manner, whereas NAG-1 induction by berberine is mediated by multiple signaling pathways. Our results suggest that berberine facilitates apoptosis and that NAG-1 and ATF3 expression plays an important role in berberine-induced apoptosis.
Coscinium fenestratum (Gaertn.) Colebr. (Menispermaceae), called "Hamm" in Thai, is a traditional... more Coscinium fenestratum (Gaertn.) Colebr. (Menispermaceae), called "Hamm" in Thai, is a traditional medicine of the northeastern part of Thailand which is recently very popularly used. Its stem is claimed to be effective against several symptoms. The major components in the stem of this plant are isoquinoline alkaloids such as berberine, palmatine, tetrahydropalmatine, crebanine and jatrorrhizine. At present, berberine content in C. fenestratum has not been reported elsewhere. In the present study berberine content in the stem of this plant was examined. Ten samples of the dried stems were purchased from ten different traditional drugstores from various parts of the country. Extracts of these samples were prepared by maceration with 80% ethanol and the berberine content of each sample was determined by TLCdensitometry. Yields of the crude extracts were in the range of 9.87-16.38% dry weight while berberine contents in the dried powder and in the crude extract were in the ranges of 1.71-2.89% w/w and 11.84-18.45% dry weight, respectively. Thin layer chromatographic fingerprints of each extract showed similar pattern with bands of berberine as the major alkaloid and other minor alkaloids. ©All right reserved.
Evidence-Based Complementary and Alternative Medicine, 2015
The in vitro antioxidant and antibacterial assays against clinically isolated Streptococcus suis ... more The in vitro antioxidant and antibacterial assays against clinically isolated Streptococcus suis and Staphylococcus intermedius of the extracts prepared by decoction and ethanolic reflux of different parts of Chettaphangki (Cladogynos orientalis Zipp. ex Span), including the leaves, roots, and stems, using 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging assay and disc diffusion method were conducted. Quantitative analysis of total phenolic and total flavonoid contents in the extracts using spectrophotometric methods was also performed. Finally, phytochemical screening by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC) was conducted. Leaf ethanolic reflux extract (100 g) contained the highest total phenolic and total flavonoid contents of 7.21 ± 0.28 μg gallic acid equivalent (GAE) and 11.51 ± 2.02 μg rutin equivalent (RE), respectively. Chettaphangki extracts promoted low antioxidant activity with EC50 values in the range of 0.27-0.48 mg/mL. Extracts and fractions from the roots and stems of this plant promoted low to intermediate antibacterial activity against S. intermedius with the inhibition zones between 7 and 14 mm. The chromatographic data suggested that the leaf extracts of C. orientalis contained rutin while the root and stem extracts contained scopoletin and chettaphanin I. Rutin promoted strong antioxidant activity while chettaphanin I showed low antibacterial activity against Staphylococcus intermedius.
Experimental and therapeutic medicine, 2010
Coscinium fenestratum (Gaertn.) Colebr. is traditionally used for the treatment of cancer, arthri... more Coscinium fenestratum (Gaertn.) Colebr. is traditionally used for the treatment of cancer, arthritis and diabetes mellitus. The purpose of this study was to determine the molecular mechanisms by which this plant shows beneficial effects. An 80% ethanolic extract of C. fenestratum (80ET) was separated by its polarity into dichloromethane (DCM) and aqueous fractions (WF), and the anti-proliferative effects of 80ET, DCM and WF were investigated. Berberine, one of the major components of C. fenestratum, was used as a control. The 80ET, DCM, WF and berberine showed anti-proliferative activity as assessed by cell growth assay. Subsequently, the pro-apoptotic proteins NAG-1 and ATF3 were increased and the cell cycle protein cyclin D1 was decreased by the extract and its fractions. Interestingly, only the DCM fraction exhibited the induction of peroxisome proliferator-activated receptor γ (PPARγ) binding activity, which represents a pro-apoptotic activity in colorectal cancer cells. The ove...
Pharmaceutical Biology, 2015
Abstract Context: Thunbergia laurifolia Lindl. (Acanthaceae) is a Thai medicinal plant used for t... more Abstract Context: Thunbergia laurifolia Lindl. (Acanthaceae) is a Thai medicinal plant used for the detoxification of poison which is likely to be beneficial for the treatment of cognitive deficits including Alzheimer's disease. Objective: To elucidate the effects of Thunbergia laurifolia leaf extract (TLL) on cognitive dysfunction and depression-like behavior in olfactory bulbectomized mice (OBX). Materials and methods: OBX mice were treated daily with TLL at the dose of 250 and 500 mg/kg, tacrine, and imipramine, on the day after 10 d of OBX operation. The effects of TLL on cognitive and depression-like behavior of the animals were analyzed. After completing behavioral experiments, the expression levels of cholinergic marker genes encoding ChAT and muscarinic M1 receptor were quantitatively analyzed. Results: TLL and tacrine reduced OBX-induced cognitive deficits in the object recognition test (ORT) with the time spent for the novel object two times longer than that of the familiar object. Moreover, TLL at the dose of 500 mg/kg and imipramine ameliorated depression-like behavior in the tail suspension test (TST) by reducing the duration of immobility from 25.18% to 3.16% and from 25.18% to 6.48%, respectively. TLL at the dose of 250 and 500 mg/kg reversed the OBX-induced down-regulation of ChAT mRNA expression in the hippocampus from 0.12 to 0.17 and 0.24, respectively, while the down-regulation of mRNA expression of muscarinic M1 receptor was also reversed by TLL from 0.23 to 0.38 and 0.48, respectively. Conclusions: TLL ameliorates non-spatial short-term memory deficits in OBX mice, and has the potential to exhibit an antidepressant-like action.
Planta Medica, 2014
ABSTRACT Thai traditional anti-diabetic herbal formula, Mathura Meha, composed of 26 Thai medicin... more ABSTRACT Thai traditional anti-diabetic herbal formula, Mathura Meha, composed of 26 Thai medicinal plants, has been used as alternative and complementary medicine for diabetes treatment in Wang-nam-yen hospital, a model hospital of Thai traditional medicine established by Ministry of Public Health. It is interesting that the formula could control blood glucose level of patients who didn’t respond to conventional hypoglycemic drugs or insulin injection. To provide scientific evidences of efficacy and safety of this herbal formula, in vivo anti-diabetic activity and acute toxicity were investigated. The herbal formula was extracted by 3 different methods, percolation with 80% and 50% ethanol, and water decoction. Single dose oral administration experiments [1] revealed that among 3 extracts, aqueous extract was the most effective extract. It significantly decreased plasma glucose level of streptozotocin-nicotinamide induced diabetic rats [2] at a dose of 50 mg/kg during oral glucose tolerant test (OGTT). Daily oral administration of 25 and 50 mg/kg aqueous extract for 2 weeks [1] significantly lowered 2 hours postprandial plasma glucose level (2h-PPG) of diabetic rats for 8.97% and 11.51%, respectively. There were no sign or symptom of toxicity observed after oral administration of aqueous extract (5 g/kg) [1] to male and female rats for 24 hours and no mortality was observed up to 14 days of monitoring.
Medical Principles and Practice, 2006
To develop the optimal extraction procedure (i.e. maceration, percolation or Soxhlet extraction) ... more To develop the optimal extraction procedure (i.e. maceration, percolation or Soxhlet extraction) and thin- layer chromatographic (TLC)-densitometric method for the determination of berberine content of Coscinium fenestratum. Maceration, percolation and Soxhlet extraction techniques were used to extract alkaloids from dried stems of C. fenestratum. The solvents used were 50 and 80% ethanol. Crude extracts and berberine content recovered from the TLC fingerprint were evaluated for chemical components of each extraction method. Precoated silica gel GF(254) plates were used as stationary phase while butanol:glacial acetic acid:water (14:3:4) was used as a mobile phase. Detection and quantitation of berberine were performed by densitometry at the wavelength of 415 nm over the linearity range of 240-840 ng (r(2) = 0.9982). The relative standard deviations from intraday and interday precisions were less than 4.13%. The recovery of standard berberine was 97.58-98.71% (%RSD = 3.85), and the limit of detection and quantitation were 25 and 50 ng/spot, respectively. Eighty percent ethanol gave a higher content of berberine than 50% ethanol. Berberine contents from maceration, percolation and Soxhlet extraction with 80% ethanol were 3.37+/- 0.30, 3.08+/- 0.38 and 2.67+/- 0.27% w/w, respectively. The TLC-densitometric method was simple, accurate and precise for quantitating berberine in the stem extract of C. fenestratum. Maceration with 80% ethanol gave the highest content of berberine in the extract. TLC of the extracts from different methods showed a similar pattern.
Life Sciences, 2012
The aims of the present study were to investigate the effect of crebanine on memory and cognition... more The aims of the present study were to investigate the effect of crebanine on memory and cognition impairment in mice and to elucidate the underlying molecular mechanisms. The memory-enhancing effects of crebanine were assessed with a water maze test using scopolamine-induced amnesic mice. The molecular mechanism was explored in silico by docking crebanine against acetylcholine binding proteins (AChBPs) and in vitro with a radioligand competition assay using (±)-[(3)H]-epibatidine. The pharmacological behavior was assessed by observing changes to the functional activity of α7-nAChRs expressed in Xenopus oocytes and by fluorescent assays on recombinant ligand gated ion channel (LGIC) receptors expressed in mammalian cells. The administration of crebanine significantly improved the cognitive deficits induced by scopolamine, as measured by the water maze test. The docking results demonstrated that crebanine bound to the active binding site of the AChBP template with a good docking energy. Crebanine significantly inhibited the binding of (±)-[(3)H]-epibatidine to AChBPs with K(i) values of 179 nM and 538 nM for Ls and Ac, respectively. Further functional assays performed using two separate protocols indicated that crebanine is an antagonist of the α7-nAChR with an IC(50) of 19.1μM. The observed actions of crebanine against amnesia and its effect on α7-nAChRs will be beneficial for target-based drug design; crebanine or its scaffold can be used as the starting point to develop a drug for Alzheimer's disease. The cognition-enhancing effects of crebanine and the underlying mechanism based on α7-nAChRs are consistent with its traditional use. These findings demonstrate the potential utility of crebanine in the development of neurodegenerative therapy.
Journal of Biomolecular Screening, 2012
The nicotinic acetylcholine receptors (nAChRs) are a member of the ligand-gated ion channel famil... more The nicotinic acetylcholine receptors (nAChRs) are a member of the ligand-gated ion channel family and play a key role in the transfer of information across neurological networks. The X-ray crystal structure of agonist-bound α 7 acetylcholine binding protein (AChBP) has been recognized as the most appropriate template to model the ligand-binding domain of nAChR for studying the molecular mechanism of the receptor-ligand interactions. Virtual screening of the National Cancer Institute diversity set, a library of 1990 compounds with nonredundant pharmacophore profiles, using AutoDock against AChBPs revealed 51 potential candidates. In vitro radioligand competition assays using [ 3 H] epibatidine against the AChBPs from the freshwater snails, Lymnaea stagnalis, and from the marine species, Aplysia californica and the mutant (AcY55W), revealed seven compounds from the list of candidates that had micromolar to nanomolar affinities for the AChBPs. Further investigation on α 7 nAChR expressing in Xenopus oocytes and on the recombinant receptors with fluorescence resonance energy transfer (FRET)-based calcium sensor expressing in HEK cells showed that seven compounds were antagonists of α 7 nAChR, only one compound (NSC34352) demonstrated partial agonistic effect at low dose (10 µM), and two compounds (NSC36369 and NSC34352) were selective antagonists on α 7 nAchR with moderate potency. These hits serve as novel templates/scaffolds for development of more potent and specific in the AChR systems.
Evidence-Based Complementary and Alternative Medicine, 2013
Acanthopanax trifoliatus is a plant that has been traditionally used in Thailand as a vegetable a... more Acanthopanax trifoliatus is a plant that has been traditionally used in Thailand as a vegetable and a tonic. This study investigated effects of the aqueous extract of its leaves (ATL) on cognitive and emotional deficits using an olfactory bulbectomized mouse (OBX) model. OBX mice were treated daily with ATL (250 and 500 mg/kg, p.o.) 3 days after OBX. Antidementia drug tacrine (2.5 mg/kg/day) and antidepressant drug imipramine (10 mg/kg/day) were given i.p. as reference drugs. OBX significantly impaired cognitive behavior in a novel object recognition test and a modified Y-maze test and induced depression-like behavior in a tail suspension test. ATL and tacrine treatment attenuated OBX-induced cognitive deficits, whereas ATL and imipramine improved OBX-induced depression-like behavior. Neurochemical studies conducted after completing behavioral experiments demonstrated that OBX downregulated the expression levels of cholinergic marker genes encoding choline acetyltransferase and muscarinic M 1 receptor in a manner reversed by ATL and tacrine. Moreover, ATL and tacrine administration inhibited the ex vivo activity of acetylcholinesterase in the brain. These findings suggest that ATL is beneficial for the treatment of cognitive and emotional deficits related to dementia with depressive symptoms and that the antidementia effect of ATL is mediated by normalizing the function of central cholinergic systems.
Carbohydrate Polymers, 2009
The objective of this study was to examine the effects of different storage conditions of star fr... more The objective of this study was to examine the effects of different storage conditions of star fruit (Averrhoa carambola) juice on the activity of acetylcholinesterase in various organs of Sprague Dawley (SD) rats. The effect of oral administration of star fruit on serum lipid profiles was also examined in this study. A total of 15 female rats were assigned into three groups with five animals per group (n=5). The first group served as control group and given only distilled water (vehicle) while the other two groups were given different star fruit preparations, i.e. freshly prepared star fruit juice and after 3 hours storage, respectively. From the results obtained, a significant decrease in the hepatic acetylcholinesterase activity was observed in rats treated with star fruit juice. In conclusion, the star fruit juice at different storage conditions is selectively targeted on the acetylcholinesterase activity in rat liver but not in kidney and heart.
Therapeutic effects of herbal medicine depend on bioactive compounds contained in herbal preparat... more Therapeutic effects of herbal medicine depend on bioactive compounds contained in herbal preparation. The different plant species usually contain different constituents even though they are closely related species which influence their therapeutic effects. Therefore, it is important to ensure that the correct plant species will be used. Thai traditional anti-diabetic herbal formula, Mathura Meha, composed of 26 Thai medicinal plants, has been used as complementary medicine for diabetes treatment in Wang-nam-yen hospital. There were 6 problematic plants that could cause confusing in dried materials verification. Three categories of problems were substitution, confusing between vernacular and scientific names, and closely related species. To confront with these problems, the system for identification of dried material should be set up. In this study, 6 plants were each identified by comparing their microscopical characteristic and TLC chromatograms with authentic sample of all expecte...