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1.
Oroxylum indicum Vent. (O. indicum) is a tree commonly called Indian trumpet tree found in tropical countries, such as India, Japan, China, Sri Lanka, Malaysia. The chemical constituents obtained from different parts of plant include baicalein-7-O-diglucoside (Oroxylin B), baicalein-7-O-glucoside, chrysin, apegenin, prunetin, sitosterol, oroxindin, biochanin-A, ellagic acid, baicalein and its 6- and 7-glucuronides, scutellarein, tetuin, antraquinone and aloe-emodin. Various parts of the plant are used in Ayurveda and folk medicine for the treatment of different ailments such as cancer, diarrhea, fever, ulcer and jaundice. Recent in vivo and in vitro studies have indicated its antiinflammatory, antiulcer, hepatoprotective, anticancer, antioxidant, photocytotoxic, antiproliferative, antiarthritic, antimicrobial, antimutagenic and immunostimulant properties. Exhaustive literature survey reveals that there are some activities which are still not proven scientifically. This article is an attempt to compile an up-to-date and comprehensive review on O. indicum covering its traditional and folk medicinal uses, phytochemistry and pharmacology.  相似文献   

2.
Recent exceptional growth in human exposure to natural products known to originate from traditional medicine has lead to a resurgence of scientific interest in their biological effects. As a strategy for improvement of the assessment of their pharmacological and toxicological profile, scientific evidence-based approaches are being employed to appropriately evaluate composition, quality, potential medicinal activity and safety of these natural products. Using this approach, we comprehensively reviewed existing scientific evidence for known composition, medicinal uses (past and present), and documented biological effects with emphasis on clinical pharmacology and toxicology of two commonly used medicinal plants from South America with substantial human exposure from historical and current global use: Uncaria tomentosa (common name: cat’s claw, and Spanish: uña de gato), and Lepidium meyenii (common name: maca). Despite the geographic sourcing from remote regions of the tropical Amazon and high altitude Andean mountains, cat’s claw and maca are widely available commercially in industrialised countries. Analytical characterisations of their active constituents have identified a variety of classes of compounds of toxicological, pharmacological and even nutritional interest including oxindole and indole alkaloids, flavonoids, glucosinolates, sterols, polyunsaturated fatty acids, carbolines and other compounds. The oxindole alkaloids from the root bark of cat’s claw are thought to invoke its most widely sought-after medicinal effects as a herbal remedy against inflammation. We find the scientific evidence supporting this claim is not conclusive and although there exists a base of information addressing this medicinal use, it is limited in scope with some evidence accumulated from in vitro studies towards understanding possible mechanisms of action by specific oxindole alkaloids through inhibition of nuclear factor (NF)-κB activation. Although controlled clinical studies have demonstrated reduction in pain associated with cat’s claw intake in patients with various chronic inflammatory disorders, there is insufficient clinical data overall to draw a firm conclusion for its anti-inflammatory effects. An important observation was that experimental results were often dependent upon the nature of the preparation used. It appears that the presence of unknown substances has an important role in the overall effects of cat’s claw extracts is an important factor for consideration. The available animal toxicological studies did not indicate severe toxicity from oral intake of cat’s claw preparations but rather were suggestive of a low potential for acute and subacute oral toxicity, and a lack of evidence to demonstrate genotoxic potential and mutagenic activity. Maca is a clear example of a herb with substantial medicinal use in traditional herbal medicine by indigenous cultures in South America since the first recorded knowledge of it in the seventeenth century. The hypocotyls of maca are the edible part of the plant used for nutritional and proposed fertility-enhancing properties. Maca has been described to possess many other medicinal properties in traditional herbal medicine but only a few of them have been well studied scientifically. Published clinical studies of maca seem to be related to its property as a nutrient, for male fertility and for energy. There are inadequate data regarding the precise mechanism of action of maca. Some studies suggest that secondary metabolites found in maca extracts are important constituents responsible for its physiological effects. Maca has been reported in the scientific literature to have a low degree of acute oral toxicity in animals and low cellular toxicity in vitro. An important finding unveiled by this review is the importance of standardisation in quality and additional basic and clinical research to scientifically validate and understand composition, biological activity, safety and risk. Development of a comprehensive pharmacological and toxicological profile through critical evaluation of existing and future experimental data, especially carefully conducted clinical studies would facilitate the scientific evidence-based approach to understanding potential biological effects of these major traditionally based herbals in current global use.  相似文献   

3.
Recent exceptional growth in human exposure to natural products known to originate from traditional medicine has lead to a resurgence of scientific interest in their biological effects. As a strategy for improvement of the assessment of their pharmacological and toxicological profile, scientific evidence-based approaches are being employed to appropriately evaluate composition, quality, potential medicinal activity and safety of these natural products. Using this approach, we comprehensively reviewed existing scientific evidence for known composition, medicinal uses (past and present), and documented biological effects with emphasis on clinical pharmacology and toxicology of two commonly used medicinal plants from South America with substantial human exposure from historical and current global use: Uncaria tomentosa (common name: cat's claw, and Spanish: u?a de gato), and Lepidium meyenii (common name: maca). Despite the geographic sourcing from remote regions of the tropical Amazon and high altitude Andean mountains, cat's claw and maca are widely available commercially in industrialised countries. Analytical characterisations of their active constituents have identified a variety of classes of compounds of toxicological, pharmacological and even nutritional interest including oxindole and indole alkaloids, flavonoids, glucosinolates, sterols, polyunsaturated fatty acids, carbolines and other compounds. The oxindole alkaloids from the root bark of cat's claw are thought to invoke its most widely sought-after medicinal effects as a herbal remedy against inflammation. We find the scientific evidence supporting this claim is not conclusive and although there exists a base of information addressing this medicinal use, it is limited in scope with some evidence accumulated from in vitro studies towards understanding possible mechanisms of action by specific oxindole alkaloids through inhibition of nuclear factor (NF)-kappaB activation. Although controlled clinical studies have demonstrated reduction in pain associated with cat's claw intake in patients with various chronic inflammatory disorders, there is insufficient clinical data overall to draw a firm conclusion for its anti-inflammatory effects. An important observation was that experimental results were often dependent upon the nature of the preparation used. It appears that the presence of unknown substances has an important role in the overall effects of cat's claw extracts is an important factor for consideration. The available animal toxicological studies did not indicate severe toxicity from oral intake of cat's claw preparations but rather were suggestive of a low potential for acute and subacute oral toxicity, and a lack of evidence to demonstrate genotoxic potential and mutagenic activity. Maca is a clear example of a herb with substantial medicinal use in traditional herbal medicine by indigenous cultures in South America since the first recorded knowledge of it in the seventeenth century. The hypocotyls of maca are the edible part of the plant used for nutritional and proposed fertility-enhancing properties. Maca has been described to possess many other medicinal properties in traditional herbal medicine but only a few of them have been well studied scientifically. Published clinical studies of maca seem to be related to its property as a nutrient, for male fertility and for energy. There are inadequate data regarding the precise mechanism of action of maca. Some studies suggest that secondary metabolites found in maca extracts are important constituents responsible for its physiological effects. Maca has been reported in the scientific literature to have a low degree of acute oral toxicity in animals and low cellular toxicity in vitro. An important finding unveiled by this review is the importance of standardisation in quality and additional basic and clinical research to scientifically validate and understand composition, biological activity, safety and risk. Development of a comprehensive pharmacological and toxicological profile through critical evaluation of existing and future experimental data, especially carefully conducted clinical studies would facilitate the scientific evidence-based approach to understanding potential biological effects of these major traditionally based herbals in current global use.  相似文献   

4.
Aconite is one of the poisonous plants used therapeutically in practice of Ayurveda after proper treatment called as 'Shodhana'. To determine the effect of Shodhana treatment on chronic toxicity and to assess the effect of recovery period after chronic toxicity of aconite. Raw aconite (RV), urine treated aconite (SM), and milk treated aconite (SD) were administered in 6.25 mg/kg dose in Charles Foster strain albino rats for 90 days for chronic toxicity. Six rats from each were kept for another 30 days without test drugs treatment to observe recovery from chronic toxicity. RV was found to be highly toxic in chronic exposure, SM had no apparent toxicity, but SD had mild toxicity in kidney. The toxicities of RV and SD were reversible, but sudden withdrawal of SM caused adverse effects, suggestive of tapering withdrawal. Shodhana treatments remove toxic effects from raw aconite. Chronic toxicity of aconite is reversible. Confirmed the arrangement of abstract.  相似文献   

5.
Since centuries, natural compounds from plants, animals and microorganisms were used in medicinal traditions to treat various diseases without a solid scientific basis. Recent studies have shown that plants that were used or are still used in the medieval European medicine are able to provide relieve for many diseases including cancer. Here we summarize impact and effect of selected purified active natural compounds from plants used in European medieval medicinal traditions on cancer hallmarks and enabling characteristics identified by Hanahan and Weinberg. The aim of this commentary is to discuss the pharmacological effect of pure compounds originally discovered in plants with therapeutic medieval use. Whereas many reviews deal with Ayurvedic traditions and traditional Chinese medicine, to our knowledge, the molecular basis of European medieval medicinal approaches are much less documented.  相似文献   

6.

Objectives:

Nerium oleander is traditionally used in various diseases because of its medicinal properties. One of its uses is in musculoskeletal disorder. The aim of the study was to evaluate the skeletal muscle relaxant activity of the aqueous extract of Nerium oleander flowers (AENOF) in albino rats in comparison with diazepam.

Materials and Methods:

A total of 20 Swiss albino rats aged 6–7 weeks, of either sex, weighing about 100–150 g, were taken, and after acute toxicity studies two different doses were selected. The animals were divided into four different groups. The first group was kept as the control (normal saline), second as the standard (diazepam) and the remaining two groups as Test I and Test II, and given different doses of the AENOF. Skeletal muscle relaxant activity (motor coordination) on Rotarod and locomotor activity on photoactometer was performed. Statistical analysis was carried out by using analysis of variance, followed by Dunnett''s multiple comparison tests.

Results:

The result from the Actophotometer test and Rotarod test showed that the extract of AENOF significantly reduced (P < 0.05) the motor coordination of the tested animals.

Conclusions:

Our data indicates that AENOF possesses skeletal muscle relaxant activities.KEY WORDS: Actophotometer, muscle relaxant, Nerium oleander, rotarod, soxhlet apparatus  相似文献   

7.
《Pharmaceutical biology》2013,51(12):1413-1420
Context:?Gmelina arborea Roxb. (Verbenaceae) is an important medicinal plant in the traditional system of medicine of India. The plant is used in the treatment of snake-bites, fever, piles, and diabetes. However, there is little toxicological information available regarding its safety after exposure. The present study was designed to evaluate acute and repeated dose toxicity of the aqueous extract of Gmelina arborea stem bark.

Materials and methods:?In the acute toxicity test, Swiss albino mice were treated with aqueous extract (300, 2000, and 5000?mg/kg), orally. Animals were observed periodically during the first 24?h after administration of the extract, and daily thereafter for 14 days. In the repeated dose toxicity study, the aqueous extract of Gmelina arborea (300, 1000, and 2000?mg/kg per day) was administered orally for a period of 28 days in Wistar rats. The effects on body weight, food and water consumption, organ weight, hematology, clinical biochemistry, as well as histology, were studied.

Results and conclusion:?Aqueous extract did not produce mortality, changes in behavior or any other physiological activities in mice, for any of the selected doses. There were no significant differences in the body weight, organ weights and feeding habits between control and treated animals. Hematological and biochemical analysis showed no marked differences in any of the parameters examined in either the control or treated groups. Pathologically, neither gross abnormalities nor histopathological changes were observed. The aqueous extract of Gmelina arborea was found safe in acute and repeated dose toxicity studies when tested in rodents.  相似文献   

8.
The concept of "pharmacophylogeny" was proposed by Peigen Xiao in the 1980s based on long-term studies of Chinese researchers since ancient times and especially the 1950s. The complicated relationships and connectivity between kinship of medicinal plants, their chemical profiles and therapeutic utilities are consistent goals of pharmacophylogeny studies, which benefit innovative drug R&D. In the present work, we reviewed the origin and a brief history of research in this field, as well as the status quo and recent progress of pharmacophylogeny. The concept "pharmacophylogenomics" is put forward to represent the expanding utility of pharmacophylogeny in botanical drug R&D. Pharmacophylogeny and pharmacophylogenomics are the synthesis of multiple disciplines, such as chemotaxonomy, plant morphology, plant biochemistry/molecular biology and omics, etc. Medicinal plants within the same phylogenetic groups may have the same or similar therapeutic compounds/effects, thus forming the core of pharmacophylogeny, which is the scientific law summed up from practice and applied to practice after refining and sublimation. In the past, pharmacophylogeny plays a big role in looking for alternative resources of imported drugs in China. At present, it continues to play an active role in expanding medicinal plant resources, quality control/identification of herbal medicines, as well as predicting the chemical constituents or active ingredients of herbal medicine and the identification and determination of chemical constituents. In the ongoing future, it will play a bigger role in the search for new drugs, sorting out, summarizing, and improving herbal medicine experiences, thus boosting the sustainable conservation and utilization of traditional/natural?medicinal resources.  相似文献   

9.
We have started a systematic scientific study of folklore medicinal plants currently used as alternative medicine in Jamaican society. In this initial study, extracts of plants widely used by the islanders are studied for antibacterial activity against five common pathogens; Streptococcus group A, Staphylococcus aureus, Proteus mirabilis, Pseudomonas aeruginosa and Escherichia coli. These studies revealed that 25% (approx.) of the plant extracts had antimicrobial activity against at least one of the microbes used. Subsequent to these observations, extracts from Mikania micrantha were examined in detail. This led to the isolation of two sesquiterpenoids, mikanolide and dihydromikanolide, with activity against S. aureus and C. albicans. The results suggest that traditional folk medicine could be used as a guide in our continuing search for new natural products with potential medicinal properties.  相似文献   

10.
《Pharmaceutical biology》2013,51(9):1025-1030
Context: Solidago chilensis Meyen (Asteraceae) is widely used in South America in traditional medicine as an anti-inflammatory and diuretic, and to treat gastrointestinal disorders. However, no scientific evidence exists in literature to corroborate the therapeutic use of the plant. Despite its traditional uses, no reports are available on the safety of this utilization or on the relationship between the pharmacological activities and its phytochemical compounds.

Objective: This study investigates for the first time the acute toxicity and the gastroprotective effect of the aqueous extract from inflorescences of S. chilensis.

Materials and methods: The gastroprotective activity was evaluated in mice subjected to ethanol-induced gastric ulcer model at 125, 250, 400, 800, 1200, and 2000?mg/kg doses. Acute toxicity study was performed at one dose of 2000?mg/kg. At the end of the exposure behavioral and functional parameters and motor activity were assessed in all animals.

Results: Results demonstrated that the extract exhibited a significant antiulcer activity when given at 125-2000?mg/kg (P?<0.05), but did not show acute toxicity in mice treated with 2000?mg/kg p.o.

Discussion and conclusion: This study demonstrated that the oral administration of S. chilensis aqueous extract prevents the formation of gastric lesions caused by an aggressive factor as ethanol but does not produce toxicity by acute exposure in mice. These promising results support a better pharmacological study of S. chilensis as a potential antiulcerogenic species for studies targeted towards the development of antiulcerogenic agents.  相似文献   

11.
非依赖性药物治疗海洛因成瘾的临床研究(附700例报道)   总被引:3,自引:0,他引:3  
目的 为研究非依赖药物治疗海洛因成瘾,采用卡马西平和泰必利,按一定比例混匀配制成胶囊(以下称胶囊)治疗戒毒者的戒断症状。方法 用于临床前,委托贵阳医学院药理教研室进行了动物药理和毒理试验。结果 该胶囊能消除在小鼠对吗啡和海洛因依赖的戒断症状;大小鼠对胶囊无依赖性;急性和长期毒性试验表明无毒性作用。单用该胶囊治疗700例自愿戒毒者,疗程7~15天,随方3个月,采取自身对照法,比较戒毒者治疗前后的症状  相似文献   

12.
Objectives Malva sylvestris L., known as common mallow, is native to Europe, North Africa and Asia. In the Mediterranean region, this species has a long history of use as food, and due to its therapeutic relevance, some parts of this plant have been employed in traditional and ethnoveterinary medicines. The leaves in particular have been reported to have potent anti‐inflammatory, antioxidant, anti‐complementary, anticancer and skin tissue integrity activity. Additionally, an anti‐ulcerogenic effect was recently proven, demonstrating that the aqueous extract was more effective than cimetidine, a potent medicine used to treat gastric ulcers. Due to its wide use and medicinal importance, many studies have been conducted; however, the information in the literature is very extensive and disseminated, making it difficult to use. Key findings A complete review involving the ethnobotanical and scientific aspects of M. sylvestris has been made. The research has provided evidence that M. sylvestris has potential use as a medicinal plant and has highlighted a need for more studies involving clinical and toxicological aspects of its use. Summary This review can contribute to the field with its historical context, and by describing the progress made, new ideas for researchers can arise.  相似文献   

13.
Traditional medicine is gaining an increasing importance in diseases management. Besides, thyroid disease is one of the common endocrine disorders spreading at high frequency worldwide. The present work is an ethnopharmacological study aiming to identify, document and analyze aromatic and medicinal plants used in Algerian traditional medicines for thyroid disorders management. Semi-structured interviews with 120 herbalists and traditional practitioners and rural dwellers were realized in eleven locations in Algeria throughout field studies achieved from June 2017 to July 2019. Results reveal the use of 63 medicinal plants belonging to 59 genera and 34 families. The most represented botanical families were Lamiaceae, Fabaceae, Apiaceae, Amaranthaceae and Asteraceae. However, the most cited plant species were Atriplex halimus L., Bunium incrassatum (Boiss.) Amo, Nigella sativa L., Aquilaria malaccensis Lam. and Saussurea costus (Falc.) Lipsch. These species are taken alone or in mixtures of two or more ingredients from different origins such as honey, olive oil, and goat milk. Our findings revealed new therapeutic uses of 60 medicinal plants that have not been previously reported for the treatment of thyroid in Algeria. This is the first study documenting the traditional uses based on herbal medicine for thyroid management in Algeria. Our findings are relevant in the search for novel drug discovery. Obviously, it is the time to increase effective scientific studies on mechanisms of action of these medicinal plants in order to validate their popular usages.  相似文献   

14.
目的对比观察17味同批次中药饮片所制备的标准煎剂、膏粉(水提物)、超临界CO2萃取技术制备的中药配方颗粒和超临界CO2萃取物等四种制剂的急性毒性,明确超临界CO2萃取技术制备配方颗粒的安全剂量范围。方法将药物制成最大可溶浓度的水溶液,小鼠按照0.4 ml/10 g体重灌胃给药,空白对照组以同样容积的去离子水灌胃,24 h内给药3次,连续观察14 d动物出现的反应。结果在观察的14 d内,动物均未出现任何异常行为变化;体重未有减轻现象,与对照组相比,无显著差异;也无任何动物死亡;17味中药饮片不同工艺的最大给药量的临床用药剂量倍数在75.39~2 629.05倍之间。结论 17味同批次中药饮片所制备的标准煎剂、膏粉剂、超萃物和配方颗粒,均为无毒性药物,超临界萃取中药配方颗粒临床可安全使用。  相似文献   

15.
射干和川射干为中医临床常用的清热解毒药,《中国药典》中记载两味药的功效主治相同,但其植物基原、药材与饮片质量控制指标成分却完全不同。该文通过对射干和川射干的研究现状进行综述,探讨射干和川射干的清热解毒(抗炎)药效物质基础及其作用机制的研究思路,并揭示为何两味中药的功效主治基本相同却一直被单列记载的科学内涵,为建立射干和川射干的客观评价的质量标准和中医临床用药提供科学依据。  相似文献   

16.
目的对比观察17味同批次中药饮片所制备的标准煎剂、膏粉(水提物)、超临界CO2萃取技术制备的中药配方颗粒和超临界CO2萃取物等四种制剂的急性毒性,明确超临界CO2萃取技术制备配方颗粒的安全剂量范围。方法将药物制成最大可溶浓度的水溶液,小鼠按照0.4 ml/10 g体重灌胃给药,空白对照组以同样容积的去离子水灌胃,24 h内给药3次,连续观察14 d动物出现的反应。结果在观察的14 d内,动物均未出现任何异常行为变化;体重未有减轻现象,与对照组相比,无显著差异;也无任何动物死亡;17味中药饮片不同工艺的最大给药量的临床用药剂量倍数在75.39~2 629.05倍之间。结论 17味同批次中药饮片所制备的标准煎剂、膏粉剂、超萃物和配方颗粒,均为无毒性药物,超临界萃取中药配方颗粒临床可安全使用。  相似文献   

17.
Morphology, culture requirements, and medicinal effects of Androsace septentrionalis L. (Primulaceae) are described. In mice, water extracts of the plant (.5 ml/100g body weight) produced disturbances of the menstrual cycle and infertility after copulation. Histological studies showed enlargement of glandular mucosa cells and increased uterine connective tissue. Compared with controls, more corpora lutea were found in the fallopian tubes of treated animals. The plant is used in Siberian folk medicine for angina, heart diseases, epilepsy, gonorrhea, and as a contraceptive. The contraceptive and tranquilizing effects of the water extract of Androsace were evident in this experimentation.  相似文献   

18.
Shi J  Liu YL  Fang YX  Xu GZ  Zhai HF  Lu L 《Acta pharmacologica Sinica》2006,27(10):1303-1308
Traditional Chinese medicine (TCM) includes Chinese medicine and acupuncture. Chinese medicine consists of natural products including plants, animals and minerals. TCM has been practiced in China for more than 2000 years, and for the past 200 years has been used in treatment of drug addiction. Ten Chinese medicines for the treatment of opiate addiction have been approved by the Chinese State Food and Drug Administration (SFDA), and at least 6 are in clinical trials. The general therapeutic principle of Chinese medicine developed was based on its unique theory of " reinforcing healthy Qi and resolving and removing effects of toxicity". Acupuncture, another essential part of TCM, which was developed based on the principle that " functions of the human body are controlled by the ' Jing-Luo' and 'Qi-Xue'system" , has been used not only in China, but also in Europe, the USA and other countries, for controlling opiate addiction. There are some advantages in using TCM for opiate detoxification, including less harmful side effects, high safety and ideal effects in the inhibition of protracted withdrawal symptoms and relapse. Co-administration of TCM with modern medicine shows some synergistic effects in detoxification. Many TCM for detoxification also have efficacy in the rehabilitation of abnormal body functions induced by chronic drug use, including improving immune function, increasing working memory and preventing neurological disorder. Given that TCM is effective in the prevention of relapse and causes fewer side effects, it may be used widely in the treatment of opiate addiction.  相似文献   

19.
BacoMind is an enriched phytochemical composition derived from Bacopa monnieri, a common medicinal plant having multiple uses in the traditional system of medicine and particularly used as a memory enhancing agent for centuries. The plant and its extracts have been evaluated for anti-inflammatory, cardio tonic, sedative and neuro-muscular blocking activities. In view of the extensive use of this plant, BacoMind , standardized to bioactive compounds was evaluated in a series of toxicity studies, to confirm the safety of its usage. BacoMind , on single oral administration had a median lethal dose of 2,400 mg/kg in Sprague-Dawley rats. In a 14 day repeated dose oral toxicity study in rats, except for mild lowering in body weight gain in male rats, it was found to be tolerated well up to the dose of 500 mg/kg. A subchronic oral toxicity study for 90 days in rats at the dose levels of 85, 210 and 500 mg/kg did not reveal any evidence of toxicity with respect to clinical signs, neurological examination, food consumption, body weight gain, haematological and blood biochemistry parameters. The absolute and relative organ weight of vital organs did not differ significantly from that of the control. Necropsy and histopathological examination, did not reveal any remarkable and treatment related changes. A no-observed adverse effect level of 500 mg/kg body weight was established in rats.  相似文献   

20.
Rheum emodi has been used as an edible and medicinal plant in Tibet and Kashmir for a long period of time, while safety evaluation of this plant has not yet been investigated. In this study, acute and subchronic oral toxicity studies of aqueous extract of R. emodi (AERE) rhizome were conducted in SD rats. Animals were treated with a single dose of 1000, 2000, 4000 or 10,000 mg/kg of AERE in the acute toxicity. In subchronic oral toxicity, animals were randomly divided into four groups (10 rats/sex/group) and received doses of 0, 1000, 2000, and 4000 mg/kg/d of AERE for 90 days. Daily clinical observations, weekly measurement of body weight and food consumption were conducted. Blood and urine were collected on days 91 to measure changes. At necropsy, selected organs were weighed and recorded, and histological examination was performed. During the subchronic oral toxicity study, no mortality, obvious treatment-related clinical signs and urinalysis parameters were observed. Differences in weight gain, food consumption, hematology, biochemistry, relative organ weight and histopathology examinations between the treated group and the control group were not considered treatment-related. Our results indicated that the no-observed-adverse-effect level (NOAEL) for AERE was 4000 mg/kg/d in both genders.  相似文献   

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