India has a great wealth of various naturally occurring plant drugs which have great potential pharmacological activities.Datura stramonium(D.stramonium is one of the widely well known folklore medicinal herbs.The tro...India has a great wealth of various naturally occurring plant drugs which have great potential pharmacological activities.Datura stramonium(D.stramonium is one of the widely well known folklore medicinal herbs.The troublesome weed,D.stramonium is a plant with both poisonous and medicinal preperties and has been proven to have great pharmacological potential with a great utility real usage in folklore medicine.D.stromonium has been scientifically proven to contain alkaloids,tannins,carbohydrates and proteins.This plant has contributed various pharmacological actions in the scientific field of Indian systems of medicines like analgesic and antiasthmatic activities.The present paper presents an exclusive review work on the ethnomedical,phytochemical,pharmacological activities of this plant.展开更多
Datura stramonium L., a wild-growing plant of the Solanaceae family, is widely distributed and easily accessible. It contains a variety of toxic tropane alkaloids such as atropine, hyoscamine, and scopolamine. In East...Datura stramonium L., a wild-growing plant of the Solanaceae family, is widely distributed and easily accessible. It contains a variety of toxic tropane alkaloids such as atropine, hyoscamine, and scopolamine. In Eastern medicine, especially in Ayurvedic medicine, D. stramonium has been used for curing various human ailments, including ulcers, wounds, inflammation, rheumatism and gout, sciatica, bruises and swellings, fever, asthma and bronchitis, and toothache. A few previous studies have reported on the pharmacological effects of D. stramonium; however, complete information regarding the pharmacology, toxicity, ethnobotany and phytochemistry remains unclear. Ethnomedicinally, the frequent recreational abuse of D. stramonium has resulted in toxic syndromes. D. stramonium, in the form of paste or solution to relieve the local pain, may not have a deleterious effect; however, oral and systemic administration may lead to severe anticholinergic symptoms. For this reason, it is very important for individuals, mainly young people, to be aware of the toxic nature and potential risks associated with the use of this plant. This comprehensive review of D. stramonium includes information on botany, phytochemistry, pharmacology, toxicology and ethnomedicinal uses.展开更多
Background:Phyto-medicine represents a vast pool of novel drug development,but understanding their safety requires elaborate,multifaceted approaches,including toxicity studies.Objective:This study investigated the eff...Background:Phyto-medicine represents a vast pool of novel drug development,but understanding their safety requires elaborate,multifaceted approaches,including toxicity studies.Objective:This study investigated the effects of 90 days of oral administration of Datura stramonium(DSE)leaf extract in Rats.Methods:In the oral acute toxicity study,mice were treated with a single oral gavage of DSE at 500,1000,and 2000 mg·kg^(-1)/d,po and observed for signs of acute toxicity for 14 days.In the sub-chronic study,rats were randomized into four Groups(A-D).Group A received distilled water(10 mL·kg^(-1),po)while groups B-D received DSE(10,50 and 250 mg·kg^(-1)/d,po,respectively)orally for 90 days uninterrupted.Animals were weighed weekly,with food and water measured daily and relevant parameters assayed at the end of the 90days administration.Results:In acute toxicity studies,oral administration of up to 2 g·kg^(-1)/d,po of DSE did not elicit any semblance of toxicity or mortality within 24 h to 14 days.In the 90days studies,DSE(250 mg·kg^(-1)/d,po)decreased the body weight,brain weight,and food intake in female rats.DSE(10-250 mg·kg^(-1)/d,po)increased the red blood cell(RBC),packed cell volume(PCV)and hemoglobin(Hb)in both sexes.DSE(10-250 mg·kg^(-1)/d,po)increased the triglycerides(TG),cholesterol and low-density lipoprotein(LDL);and decreased HDL in both sexes.DSE(10-250 mg·kg^(-1)/d,po)increased the white blood cells(WBC)and platelets in female rats.DSE(10-250 mg·kg^(-1)/d,po)decreased the alkaline phosphatase(ALP)and alanine transaminase(ALT)in both studies.Serum urea level was decreased in both sexes.DSE(250 mg·kg^(-1)/d,po)decreased male rats’serum sodium ion levels.Liver,brain,testes and kidney showed severe lesions at 250 mg·kg^(-1)/d,po of the extract.Conclusion:D.stramonium is safe on acute exposure and relatively safe on sub-chronic oral administration.How-ever,prolonged use,especially at high doses,could cause Liver,brain and kidney toxicities;and abnormal lipid metabolism.展开更多
This study was conducted to investigate the temperature adaptability of Datura stramonium and D. stramonium var. tatual. Under 4 temperature levels,plantgrowth and pigment concentrations in leaves and stems were deter...This study was conducted to investigate the temperature adaptability of Datura stramonium and D. stramonium var. tatual. Under 4 temperature levels,plantgrowth and pigment concentrations in leaves and stems were determined, and leaf anatomic structures of D. stramonium var. tatual and D. stramonium were analyzed. The results showed that the palisade tissue thickness/sponge tissue thickness,stomatal density and stomatal index values of D. stramonium var. tatual were significantly greater than D. stramonium; the chlorophyll content/carotenoid content in leaves of D. stramonium var. tatual increased at first and decreased then, while no regularity was found in leaves of D. stramonium; and the contents of anthocyanin,flavonoids, and total phenols in stems of D. stramonium var. tatual were significantly higher than those in stems of D. stramonium. The temperature adaptability of D.stramonium var. tatual is stronger than that of D. stramonium.展开更多
Pot experiment was carried out to determine the allelopathic effects of Datura?stramonium on leaf chlorophyll content, root and shoot elongation, fresh and dry weight of two wild plant species: Cenchrus ciliaris and N...Pot experiment was carried out to determine the allelopathic effects of Datura?stramonium on leaf chlorophyll content, root and shoot elongation, fresh and dry weight of two wild plant species: Cenchrus ciliaris and Neonotonia wightii. Different concentrations (0%, 25%, 50%, 75% and 100%) from seed and leaf extracts of D. stramonium were used to investigate the allelopathic effects of D. stramonium on growth of tested species.?The total chlorophyll content of N. wightii was significantly reduced in all plants treated with both aqueous seed and leaf extracts of D. stramonium. In C. ciliaris, the total chlorophyll content was also significantly reduced for those plants treated with aqueous seed extract and leaf extract from D. stramonium. Relative to the control treatments, there was greater reduction in root and shoot length which was observed in higher concentrations of aqueous seed and leaf extracts. Fresh and dry weight of tested species significantly decreased after being treated with both seed and leaf aqueous extracts of D. stramonium. It was found that the allelopathic effect of aqueous seed and leaf extracts from D. stramonium on tested species was concentration-dependent. The inhibitory effects on all tested species increased as the concentration of both extracts increased from 0% to 100%. This study concluded that aqueous seed and leaf extract of D. stramonium have allelopathic effects on leaf chlorophyll content, root and shoot length, fresh and dry weight of grass (C. ciliaris) and legume (N. wightii) species.展开更多
Aim: Datura stramonium (DS) is a known hallucinogen and depressant of the central nervous system, but it is commonly used in alcoholic beverages to increase intoxication. Pharmacological, physiological and ultra-struc...Aim: Datura stramonium (DS) is a known hallucinogen and depressant of the central nervous system, but it is commonly used in alcoholic beverages to increase intoxication. Pharmacological, physiological and ultra-structural studies have demonstrated the neurotoxicity of this drug inanimals and humans at high doses. The present study investigated the histological patterns of neurodegeneration of frontal cortex (FC) neurons in Wistar rats treated with high doses of DS seed extract. Materials and methods: Ethanolic extract of DS dried seeds was diluted in normal saline and administered to male and female Wistar rats weighing 200 g - 250 g. The animals were first placed in three groups which were further sub-divided into four sub-groups. The treated sub-groups received intraperitoneal administration (i.p.) of 750 mg/kg of diluted DS seed extract once daily in group 1, twice daily (1500 mg/kg/day) in group 2 and thrice daily (2250 mg/kg/day) in group 3. The treatment was carried out for 4 weeks while the control groups received normal saline during the same period. The rats were euthanized and sections of the frontal cortices of the brain were histologically processed from all groups. Silver impregnation stain for degenerating axons and neurons was used to elucidate the pattern of degeneration induced by DS seed extract on the neurons of the FC. Results: The results of intraperitoneal administration of DS extract showed no changes in groups 1 & 2 treated rats while group 3 showed a significant pattern of histological changes like axonal atrophy, vacuolization and neuronal deaths in the frontal cortices neurons compared to the controls. Conclusion: DS may have a specific pattern of neurodegeneration at higher doses of administration. This could provide a useful model in understanding how DS intoxication can affect frontal cortex neurons with an implication of neurological disorders, mental diseases and behavioural deficits.展开更多
Background: cAMP response element-binding protein (CREB) is one of the cellular transcription factors found in neurons. CREB is also important for the survival of neurons, and has an important role in the development ...Background: cAMP response element-binding protein (CREB) is one of the cellular transcription factors found in neurons. CREB is also important for the survival of neurons, and has an important role in the development of drug addiction. Datura stramonium (DS) is a tropical ubiquitous plant commonly used to increase the intoxication of certain beverages for recreational purposes. The seeds of this plant are very toxic and may produce addiction on prolong usage. This research investigated the effects of administration of high doses of DS seeds on the expression of CREB protein in both male and female rats’ frontal cortices and its implication in addiction and neurodegeneration. Materials and Methods: The study was conducted with a total of 24 male and female Wistar rats weighing 200 g - 250 g. The rats were divided into three groups of 8 rats each. Each group was further divided into four sub-groups of 2 rats each. Ethanolic dried seed extract of DS was diluted in normal saline and administered intraperitoneally (i.p.) to the treatment groups. The treated sub-groups received 750 mg/kg of DS extract<sup> </sup>once in group 1, twice in group 2 and thrice in group 3 daily for 4 weeks respectively, while the control sub-groups received i.p. normal saline concurrently for the same duration of time. The rats were euthanized and an analysis of variance (ANOVA) was computed to detect a significant main difference of DS effect on CREB expression for each group, while post hoc Bonferroni Test compared CREB protein expression between male and female groups. Result: There were significant differences in the expression of CREB protein between the sub-groups and between the male and female rats of treated sub-group (p < 0.05) compared to the controls. There was a decrease in the female treated sub-groups and an increase in the male treated sub-groups compared to the respective controls. Conclusion: High doses of DS administration for a prolong time may affect the expressions of CREB protein differently in male and female treated rats which may consequently lead to addiction and neurodegeneration affecting frontal cortex neurons.展开更多
Polyamines play an important role in plant response to abiotic stress. S-adenosyl-1-methionine decarboxylase (SAMDC) is one of the key regulatory enzymes in the biosynthesis of polyamines. In order to better understan...Polyamines play an important role in plant response to abiotic stress. S-adenosyl-1-methionine decarboxylase (SAMDC) is one of the key regulatory enzymes in the biosynthesis of polyamines. In order to better understand the effect of regulation of polyamine biosynthesis on the shelf life improvement of litchi fruit, SAMDC cDNA isolated from Datura stramonium cloned in pBI121 was introduced into litchi genome by means of Agrobacterium tumefaciens through zygote disc transformation. Transgene and its expression are confirmed by Southern and Northern blot analyses, respectively. Transgenic plants expressing Datura SAMDC produced 1.7- to 2.4-fold higher levels of spermidine and spermine than wildtype plants under normal environmental condition, which indicated that the transgenic litchi presented an enhanced polyamines synthesis compared to wildtype plants. Our results demonstrated clearly that increasing polyamine biosynthesis in plants may be a means of creating improved fruit shelf life germplasm.展开更多
AIM: The anti-leishmanial activity of methanolic extracts of Calendula officinalis flowers, Datura stramonium seeds, and Salvia officinalis leaves against extracellular(promastigote) and intracellular(amastigote) form...AIM: The anti-leishmanial activity of methanolic extracts of Calendula officinalis flowers, Datura stramonium seeds, and Salvia officinalis leaves against extracellular(promastigote) and intracellular(amastigote) forms of Leishmania major were evaluated in this study. METHOD: In the first stage, promastigote forms of L. major, were treated with different doses of the plant extracts in a 96-well tissue-culture microplate and IC50 values for each extract were measured with colorimetric MTT assay. In the second stage, macrophage cells were infected with L. major promastigotes. Infected macrophages were treated with plant extracts. Then the macrophages were stained with Gimsa and the number of infected macrophages and amastigotes were counted with a light microscope. RESULTS: The results indicated that the plant extracts inhibited the growth of promastigotes and amastigotes of L. major. Inhibitory concentrations(IC50) for promastigote assay were 108.19, 155.15, and 184.32 μg·mL-1 for C. officinalis flowers, D. stramonium seeds and S. officinalis, respectively. The extracts also reduced the number of amastigotes in macrophage cells from 264 for control group to 88, 97, and 102 for test groups. Although the anti-leishmanial activity of the extracts were not comparable with the standard drug, miltefosine; but they showed significant efficiency in reducing the number of amastigotes in macrophages, in comparison with the control group(P < 0.001). These plant extracts had lower toxicity compared with miltefosine. CONCLUSION: This study demonstrates the potential efficacy of the methanolic extracts of C. officinalis flowers, D. stramonium seeds, and S. officinalis leaves to control of cutaneous leishmaniasis.展开更多
文摘India has a great wealth of various naturally occurring plant drugs which have great potential pharmacological activities.Datura stramonium(D.stramonium is one of the widely well known folklore medicinal herbs.The troublesome weed,D.stramonium is a plant with both poisonous and medicinal preperties and has been proven to have great pharmacological potential with a great utility real usage in folklore medicine.D.stromonium has been scientifically proven to contain alkaloids,tannins,carbohydrates and proteins.This plant has contributed various pharmacological actions in the scientific field of Indian systems of medicines like analgesic and antiasthmatic activities.The present paper presents an exclusive review work on the ethnomedical,phytochemical,pharmacological activities of this plant.
基金supported by Dr. Katsuko Komatsu Award of Year 2008, Japan
文摘Datura stramonium L., a wild-growing plant of the Solanaceae family, is widely distributed and easily accessible. It contains a variety of toxic tropane alkaloids such as atropine, hyoscamine, and scopolamine. In Eastern medicine, especially in Ayurvedic medicine, D. stramonium has been used for curing various human ailments, including ulcers, wounds, inflammation, rheumatism and gout, sciatica, bruises and swellings, fever, asthma and bronchitis, and toothache. A few previous studies have reported on the pharmacological effects of D. stramonium; however, complete information regarding the pharmacology, toxicity, ethnobotany and phytochemistry remains unclear. Ethnomedicinally, the frequent recreational abuse of D. stramonium has resulted in toxic syndromes. D. stramonium, in the form of paste or solution to relieve the local pain, may not have a deleterious effect; however, oral and systemic administration may lead to severe anticholinergic symptoms. For this reason, it is very important for individuals, mainly young people, to be aware of the toxic nature and potential risks associated with the use of this plant. This comprehensive review of D. stramonium includes information on botany, phytochemistry, pharmacology, toxicology and ethnomedicinal uses.
文摘Background:Phyto-medicine represents a vast pool of novel drug development,but understanding their safety requires elaborate,multifaceted approaches,including toxicity studies.Objective:This study investigated the effects of 90 days of oral administration of Datura stramonium(DSE)leaf extract in Rats.Methods:In the oral acute toxicity study,mice were treated with a single oral gavage of DSE at 500,1000,and 2000 mg·kg^(-1)/d,po and observed for signs of acute toxicity for 14 days.In the sub-chronic study,rats were randomized into four Groups(A-D).Group A received distilled water(10 mL·kg^(-1),po)while groups B-D received DSE(10,50 and 250 mg·kg^(-1)/d,po,respectively)orally for 90 days uninterrupted.Animals were weighed weekly,with food and water measured daily and relevant parameters assayed at the end of the 90days administration.Results:In acute toxicity studies,oral administration of up to 2 g·kg^(-1)/d,po of DSE did not elicit any semblance of toxicity or mortality within 24 h to 14 days.In the 90days studies,DSE(250 mg·kg^(-1)/d,po)decreased the body weight,brain weight,and food intake in female rats.DSE(10-250 mg·kg^(-1)/d,po)increased the red blood cell(RBC),packed cell volume(PCV)and hemoglobin(Hb)in both sexes.DSE(10-250 mg·kg^(-1)/d,po)increased the triglycerides(TG),cholesterol and low-density lipoprotein(LDL);and decreased HDL in both sexes.DSE(10-250 mg·kg^(-1)/d,po)increased the white blood cells(WBC)and platelets in female rats.DSE(10-250 mg·kg^(-1)/d,po)decreased the alkaline phosphatase(ALP)and alanine transaminase(ALT)in both studies.Serum urea level was decreased in both sexes.DSE(250 mg·kg^(-1)/d,po)decreased male rats’serum sodium ion levels.Liver,brain,testes and kidney showed severe lesions at 250 mg·kg^(-1)/d,po of the extract.Conclusion:D.stramonium is safe on acute exposure and relatively safe on sub-chronic oral administration.How-ever,prolonged use,especially at high doses,could cause Liver,brain and kidney toxicities;and abnormal lipid metabolism.
基金Supported by the Fund Program of the State Administration of Inspection and Quarantine(2008kj41)~~
文摘This study was conducted to investigate the temperature adaptability of Datura stramonium and D. stramonium var. tatual. Under 4 temperature levels,plantgrowth and pigment concentrations in leaves and stems were determined, and leaf anatomic structures of D. stramonium var. tatual and D. stramonium were analyzed. The results showed that the palisade tissue thickness/sponge tissue thickness,stomatal density and stomatal index values of D. stramonium var. tatual were significantly greater than D. stramonium; the chlorophyll content/carotenoid content in leaves of D. stramonium var. tatual increased at first and decreased then, while no regularity was found in leaves of D. stramonium; and the contents of anthocyanin,flavonoids, and total phenols in stems of D. stramonium var. tatual were significantly higher than those in stems of D. stramonium. The temperature adaptability of D.stramonium var. tatual is stronger than that of D. stramonium.
文摘Pot experiment was carried out to determine the allelopathic effects of Datura?stramonium on leaf chlorophyll content, root and shoot elongation, fresh and dry weight of two wild plant species: Cenchrus ciliaris and Neonotonia wightii. Different concentrations (0%, 25%, 50%, 75% and 100%) from seed and leaf extracts of D. stramonium were used to investigate the allelopathic effects of D. stramonium on growth of tested species.?The total chlorophyll content of N. wightii was significantly reduced in all plants treated with both aqueous seed and leaf extracts of D. stramonium. In C. ciliaris, the total chlorophyll content was also significantly reduced for those plants treated with aqueous seed extract and leaf extract from D. stramonium. Relative to the control treatments, there was greater reduction in root and shoot length which was observed in higher concentrations of aqueous seed and leaf extracts. Fresh and dry weight of tested species significantly decreased after being treated with both seed and leaf aqueous extracts of D. stramonium. It was found that the allelopathic effect of aqueous seed and leaf extracts from D. stramonium on tested species was concentration-dependent. The inhibitory effects on all tested species increased as the concentration of both extracts increased from 0% to 100%. This study concluded that aqueous seed and leaf extract of D. stramonium have allelopathic effects on leaf chlorophyll content, root and shoot length, fresh and dry weight of grass (C. ciliaris) and legume (N. wightii) species.
文摘Aim: Datura stramonium (DS) is a known hallucinogen and depressant of the central nervous system, but it is commonly used in alcoholic beverages to increase intoxication. Pharmacological, physiological and ultra-structural studies have demonstrated the neurotoxicity of this drug inanimals and humans at high doses. The present study investigated the histological patterns of neurodegeneration of frontal cortex (FC) neurons in Wistar rats treated with high doses of DS seed extract. Materials and methods: Ethanolic extract of DS dried seeds was diluted in normal saline and administered to male and female Wistar rats weighing 200 g - 250 g. The animals were first placed in three groups which were further sub-divided into four sub-groups. The treated sub-groups received intraperitoneal administration (i.p.) of 750 mg/kg of diluted DS seed extract once daily in group 1, twice daily (1500 mg/kg/day) in group 2 and thrice daily (2250 mg/kg/day) in group 3. The treatment was carried out for 4 weeks while the control groups received normal saline during the same period. The rats were euthanized and sections of the frontal cortices of the brain were histologically processed from all groups. Silver impregnation stain for degenerating axons and neurons was used to elucidate the pattern of degeneration induced by DS seed extract on the neurons of the FC. Results: The results of intraperitoneal administration of DS extract showed no changes in groups 1 & 2 treated rats while group 3 showed a significant pattern of histological changes like axonal atrophy, vacuolization and neuronal deaths in the frontal cortices neurons compared to the controls. Conclusion: DS may have a specific pattern of neurodegeneration at higher doses of administration. This could provide a useful model in understanding how DS intoxication can affect frontal cortex neurons with an implication of neurological disorders, mental diseases and behavioural deficits.
文摘Background: cAMP response element-binding protein (CREB) is one of the cellular transcription factors found in neurons. CREB is also important for the survival of neurons, and has an important role in the development of drug addiction. Datura stramonium (DS) is a tropical ubiquitous plant commonly used to increase the intoxication of certain beverages for recreational purposes. The seeds of this plant are very toxic and may produce addiction on prolong usage. This research investigated the effects of administration of high doses of DS seeds on the expression of CREB protein in both male and female rats’ frontal cortices and its implication in addiction and neurodegeneration. Materials and Methods: The study was conducted with a total of 24 male and female Wistar rats weighing 200 g - 250 g. The rats were divided into three groups of 8 rats each. Each group was further divided into four sub-groups of 2 rats each. Ethanolic dried seed extract of DS was diluted in normal saline and administered intraperitoneally (i.p.) to the treatment groups. The treated sub-groups received 750 mg/kg of DS extract<sup> </sup>once in group 1, twice in group 2 and thrice in group 3 daily for 4 weeks respectively, while the control sub-groups received i.p. normal saline concurrently for the same duration of time. The rats were euthanized and an analysis of variance (ANOVA) was computed to detect a significant main difference of DS effect on CREB expression for each group, while post hoc Bonferroni Test compared CREB protein expression between male and female groups. Result: There were significant differences in the expression of CREB protein between the sub-groups and between the male and female rats of treated sub-group (p < 0.05) compared to the controls. There was a decrease in the female treated sub-groups and an increase in the male treated sub-groups compared to the respective controls. Conclusion: High doses of DS administration for a prolong time may affect the expressions of CREB protein differently in male and female treated rats which may consequently lead to addiction and neurodegeneration affecting frontal cortex neurons.
文摘Polyamines play an important role in plant response to abiotic stress. S-adenosyl-1-methionine decarboxylase (SAMDC) is one of the key regulatory enzymes in the biosynthesis of polyamines. In order to better understand the effect of regulation of polyamine biosynthesis on the shelf life improvement of litchi fruit, SAMDC cDNA isolated from Datura stramonium cloned in pBI121 was introduced into litchi genome by means of Agrobacterium tumefaciens through zygote disc transformation. Transgene and its expression are confirmed by Southern and Northern blot analyses, respectively. Transgenic plants expressing Datura SAMDC produced 1.7- to 2.4-fold higher levels of spermidine and spermine than wildtype plants under normal environmental condition, which indicated that the transgenic litchi presented an enhanced polyamines synthesis compared to wildtype plants. Our results demonstrated clearly that increasing polyamine biosynthesis in plants may be a means of creating improved fruit shelf life germplasm.
文摘AIM: The anti-leishmanial activity of methanolic extracts of Calendula officinalis flowers, Datura stramonium seeds, and Salvia officinalis leaves against extracellular(promastigote) and intracellular(amastigote) forms of Leishmania major were evaluated in this study. METHOD: In the first stage, promastigote forms of L. major, were treated with different doses of the plant extracts in a 96-well tissue-culture microplate and IC50 values for each extract were measured with colorimetric MTT assay. In the second stage, macrophage cells were infected with L. major promastigotes. Infected macrophages were treated with plant extracts. Then the macrophages were stained with Gimsa and the number of infected macrophages and amastigotes were counted with a light microscope. RESULTS: The results indicated that the plant extracts inhibited the growth of promastigotes and amastigotes of L. major. Inhibitory concentrations(IC50) for promastigote assay were 108.19, 155.15, and 184.32 μg·mL-1 for C. officinalis flowers, D. stramonium seeds and S. officinalis, respectively. The extracts also reduced the number of amastigotes in macrophage cells from 264 for control group to 88, 97, and 102 for test groups. Although the anti-leishmanial activity of the extracts were not comparable with the standard drug, miltefosine; but they showed significant efficiency in reducing the number of amastigotes in macrophages, in comparison with the control group(P < 0.001). These plant extracts had lower toxicity compared with miltefosine. CONCLUSION: This study demonstrates the potential efficacy of the methanolic extracts of C. officinalis flowers, D. stramonium seeds, and S. officinalis leaves to control of cutaneous leishmaniasis.