Objective: To investigate the toxicity of aqueous extract of Guibourtia tessmannii(Harms) J. Leonard(G. tessmannii) and evaluate its safety.Methods: NMRI mice were used to determine the acute toxicity of G. tessmannii...Objective: To investigate the toxicity of aqueous extract of Guibourtia tessmannii(Harms) J. Leonard(G. tessmannii) and evaluate its safety.Methods: NMRI mice were used to determine the acute toxicity of G. tessmannii.Increasing concentrations of the plant extracts were administered intraperitoneally or by force-feeding. General behavior and death were monitored and recorded daily for 7 days.In order to determine the sub-acute toxicity of the extract, several doses were administered by oral gavage daily for 28 days in adult Wistar rats. Different parameters were assessed including body weight, food and water intake, biochemical parameters and several vital organ weights.Results: LD50 of 328.78 mg/kg was obtained by i.p. route and more than 5 000 mg/kg was obtained in acute toxicity by oral route. In sub-acute toxicity, no significant alteration was observed in body weight or vital organs, food and water intake, and biochemical parameters.Conclusions: The results showed that the aqueous extract of G. tessmannii has low toxicity intraperitoneally and no sub-acute toxicity via oral intake.展开更多
OBJECTIVE Currently, almost all chemical compounds or biological reagents to reverse or slow down the AD process have failed in clinical trials. An integrative and multi-targeted strategy is increasingly appreciated t...OBJECTIVE Currently, almost all chemical compounds or biological reagents to reverse or slow down the AD process have failed in clinical trials. An integrative and multi-targeted strategy is increasingly appreciated to effectively combat this devastating disease. Traditional Chinese medicine(TCM) has been widely used for treatment of dementia, and thus the advantages of the potential therapeutic features of TCM treatment and associated mechanisms should be well taken. The Amnesia Remedy Formula(ARF) was invented by one of the most influential Master of TCM SUN Si-miao, who lived for about 100 year old. The aim of this research is to characterize the time course changes of the cognitive behaviors post a ARF, and the mechanism underlying the effects, focusing on PKA-centered signaling for both enhancement of neural plasticity and clearance of the phosphorylated Tau. RESULTS We tested the efficacy of ARF on two animal models of AD, and examine the central role of PKA signaling in the enhancement of neural plasticity via PKA/CREB/BDNF pathway as well as clearance of toxic p Tau via PKA/GSK3β/p Tau pathway. In the scopolamine model, ARF effectively reversed the memory in Morris water maze(MWM) test, with some features superior to anti-AD drug donepezil. In a battery test of MWM, novel object recognition or T maze in 5-month-old senescenceaccelerated mouse prone 8(SAMP8) strain mice, two weeks of administration of ARF showed overall better improvement in memory loss than donepezil, and the effect lasted for at least 1 week after termination of administration of the formula. ARF increased expression of PKA/CREB/BDNF and synaptic proteins PSD95 expression, as well as enhanced Ser9 phosphorylation of GSK3β, thus reduced p Tau in the hippocampus. Blockade of PKA signaling blunted the anti-AD-like effect of ARF, with reversal of CREB/BDNF signaling. Transcriptomic analysis indicated some changes of novel molecules along this pathway may be part of the pathological and therapeutic mechanism, which warrants further investigation. CONCLUSION ARF may display some advantageous features in treating AD with early onset, via multi-targeted manner including enhancement of neural plasticity and reduction in Tau toxicity.展开更多
[ Objective] A histological study was conducted to investigate the toxicity of "Baikening" and the toxic effect of "Baikening" on roosters after longer- term administration at different dose levels. [ Method] Thir...[ Objective] A histological study was conducted to investigate the toxicity of "Baikening" and the toxic effect of "Baikening" on roosters after longer- term administration at different dose levels. [ Method] Thirty 21-day-old Hy-Line Brown roosters were administered with 0.5 and 1.0 ml of "Balkening" aqueous extract through drinking water once a day for continuous 14 d. Roosters in control group and experimental groups after drug administration for 14 d and drug with- dmwal for 7 d were euthatfized; livers, kidneys, thymuses, spleens and bursas of Fabricius were collected and weighed for comparative analysis. Various tissues were prepared into paraffin-embedded slices and stained by H. E. , to observe histological changes of various organs under an optical microscope. [ Result ] After drug administration for 14 d, all the roosters in experimental groups survived; there was no visible pathological change in various organs of Hy-Line Brown roosters in each group; organ weights of Fly-Line Brown roosters in various groups showed no significant difference; observation results of tissue slices indicated that there was no pathological change in fine structures, nuclei and cytoplasm of various organs of Hy-Line Brown roosters in different groups ; various blood vessels in different organs also presented no change in blood circulation or other pathological changes. [ Conclusion] "Baikening" aqueous extract (oral administration) has no toxic and side effect on roosters in the subacute toxicity experiment.展开更多
According to the World Health Organization’s world report on hearing,nearly 2.5 billion people worldwide will suffer from hearing loss by 2050,which may contribute to a severe impact on individual life quality and na...According to the World Health Organization’s world report on hearing,nearly 2.5 billion people worldwide will suffer from hearing loss by 2050,which may contribute to a severe impact on individual life quality and national economies.Sensorineural hearing loss(SNHL)occurs commonly as a result of noise exposure,aging,and ototoxic drugs,and is pathologically characterized by the impairment of mechanosensory hair cells of the inner ear,which is mainly triggered by reactive oxygen species accumulation,inflammation,and mitochondrial dysfunction.Though recent advances have been made in understanding the ability of cochlear repair and regeneration,there are still no effective therapeutic drugs for SNHL.Chinese herbal medicine which is widely distributed and easily accessible in China has demonstrated a unique curative effect against SNHL with higher safety and lower cost compared with Western medicine.Herein we present trends in research for Chinese herbal medicine for the treatment of SNHL,and elucidate their molecular mechanisms of action,to pave the way for further research and development of novel effective drugs in this field.展开更多
Background:Globally,80%people use plant-derived products for treating or preventing diseases.One prevalent perception about medicinal plants is that they are safe and devoid of adverse effects.However,approximately 1,...Background:Globally,80%people use plant-derived products for treating or preventing diseases.One prevalent perception about medicinal plants is that they are safe and devoid of adverse effects.However,approximately 1,50,000 plants contain toxic substances.Objective:The present review focuses on medicinal plant extracts/fractions toxicity assessments made in preclin-ical models by oral route.Methods:Detail studies were searched from databases including PubMed and Google Scholar.A manual reference screening of the selected studies was done to identify relevant articles,with no language restriction being imposed at the time of searching.Results:The studies included were performed in rodents,and the test substances were administered orally.Our search revealed 33 widely used plants or products with significant toxicity,and phytochemicals from these plants have been summarized.Through a systematic review,we identified a plethora of medicinal plant extracts reporting safety and toxicity concerns.Conclusion:In the future,preclinical toxicokinetic studies of herbs and the determination of their no-observed-adverse-effect levels are required for a complete safety assessment.Finally,the interaction of herbs with com-monly used/over-the-counter drugs in terms of the latter’s metabolic profile should be undertaken.展开更多
Objective:This paper discusses the composition of prescription qualitative,quantitative design principles and methods based on herbal property combination,describing the method application in new prescription design.M...Objective:This paper discusses the composition of prescription qualitative,quantitative design principles and methods based on herbal property combination,describing the method application in new prescription design.Method:Qualitative property-combination pattern(PP)calculation was based on bipartite graphing and performing a greedy algorithm which was designed to optimize obtaining a new herbal prescription.Quantitative PP calculation was based on the qualitative computation.To calculate the Euclidean distance for the PP of the new prescription,an optimized algorithm for solving the unknown minimum Euclidean distance was used with,the new weighted proportions.Finally,non-linear optimization software was used to find the minimum Euclidean distance.Results:Using the PP of classic prescription Large Yin-Nourishing Pill,applying quantitative PP calculation a new prescription was created.Mathematical algorithms based on property combinations of traditional Chinese herbs can be applied to identify compatibility and synergies of herbs within prescriptions,especially classic formulas.Conclusion:In silico methods can then be used to create new prescriptions or modify existing ones depending on need.This type of automated approach may increase efficiency in designing new drugs based on Chinese herbs.展开更多
The safety issue on herbal and traditional medicines(H&TM) is one of the most challenging problems and serious concern worldwide. With scientific endeavor and further exploration, we came to realize that there are...The safety issue on herbal and traditional medicines(H&TM) is one of the most challenging problems and serious concern worldwide. With scientific endeavor and further exploration, we came to realize that there are great differences between H&TM and synthetic drugs in many aspects, such as medical theory, medication experience, compatibility, processing, toxicological characteristics, and safety evaluating requirements. In the current preclinical models for synthetic drugs, the safety assessment results of some conventional deemed 'nontoxic' H&TM were not well consistent with clinical situations, which resulted in major difficulties to understand the mechanisms and guide the safe and rational uses of these H&TM. Thus, based on the traditional Chinese medicine toxicity theory called You Gu Wu Yun, this paper introduces a novel safety assessment strategy for H&TM, named as disease-based toxicology. It aims to cognize the relativity and susceptibility of the toxicity of H&TM, and then to enhance controllability in new drug development and clinical applications. It also provides a theoretical practice for the traditional Chinese medicine toxicity theory and a methodological promotion for the future development of the precision toxicology for H&TM.展开更多
Objective: To obtain fundamental information for the standardization of herbal medicine in Korea. Methods: We analyzed the herbal medicine prescription data of patients at the Pusan National University Korean Medici...Objective: To obtain fundamental information for the standardization of herbal medicine in Korea. Methods: We analyzed the herbal medicine prescription data of patients at the Pusan National University Korean Medicine Hospital from March 2010 to February 2013. We used the Dongui-Bogam (Dong Yi Bao Jian) to classify prescribed herbal medicines. Results: The study revealed that the most frequently prescribed herbal medicine was ‘Liuwei Dihuang Pill (LWDHP, 六味地黄丸)' which was used for invigorating ‘Shen (Kidndy)-yin'. ‘LWDHP' was most frequently prescribed to male patients aged 50-59, 60-69, 70-79 and 80-89 years, and ‘Xionggui Tiaoxue Decoction (XGTXD, 芎归调血饮)' was most frequently prescribed to female patients aged 30-39 and 40-49 years. According to the International Classification of Diseases (ICD) codes,‘Diseases of the musculoskeletal system and connective tissue' showed the highest prevalence. ‘LWDHP' and 'XGTXD' was the most frequently prescribed in categories 5 and 3, respectively. Based on the percentage of prescriptions for each sex, ‘Ziyin Jianghuo Decoction (滋阴降火汤)' was prescribed to mainly male patients, and ‘XGTXD' with ‘Guima Geban Decoction (桂麻各半汤)' were prescribed to mainly female patients. Conclusion: This study analysis successfully determined the frequency of a variety of herbal medicines, and many restorative herbal medicines were identified and frequently administered.展开更多
基金Supported by the doctoral training funds no.84722652USTM/4802 AC-USTM,of the University of Sciences and Technique of Masuku
文摘Objective: To investigate the toxicity of aqueous extract of Guibourtia tessmannii(Harms) J. Leonard(G. tessmannii) and evaluate its safety.Methods: NMRI mice were used to determine the acute toxicity of G. tessmannii.Increasing concentrations of the plant extracts were administered intraperitoneally or by force-feeding. General behavior and death were monitored and recorded daily for 7 days.In order to determine the sub-acute toxicity of the extract, several doses were administered by oral gavage daily for 28 days in adult Wistar rats. Different parameters were assessed including body weight, food and water intake, biochemical parameters and several vital organ weights.Results: LD50 of 328.78 mg/kg was obtained by i.p. route and more than 5 000 mg/kg was obtained in acute toxicity by oral route. In sub-acute toxicity, no significant alteration was observed in body weight or vital organs, food and water intake, and biochemical parameters.Conclusions: The results showed that the aqueous extract of G. tessmannii has low toxicity intraperitoneally and no sub-acute toxicity via oral intake.
文摘OBJECTIVE Currently, almost all chemical compounds or biological reagents to reverse or slow down the AD process have failed in clinical trials. An integrative and multi-targeted strategy is increasingly appreciated to effectively combat this devastating disease. Traditional Chinese medicine(TCM) has been widely used for treatment of dementia, and thus the advantages of the potential therapeutic features of TCM treatment and associated mechanisms should be well taken. The Amnesia Remedy Formula(ARF) was invented by one of the most influential Master of TCM SUN Si-miao, who lived for about 100 year old. The aim of this research is to characterize the time course changes of the cognitive behaviors post a ARF, and the mechanism underlying the effects, focusing on PKA-centered signaling for both enhancement of neural plasticity and clearance of the phosphorylated Tau. RESULTS We tested the efficacy of ARF on two animal models of AD, and examine the central role of PKA signaling in the enhancement of neural plasticity via PKA/CREB/BDNF pathway as well as clearance of toxic p Tau via PKA/GSK3β/p Tau pathway. In the scopolamine model, ARF effectively reversed the memory in Morris water maze(MWM) test, with some features superior to anti-AD drug donepezil. In a battery test of MWM, novel object recognition or T maze in 5-month-old senescenceaccelerated mouse prone 8(SAMP8) strain mice, two weeks of administration of ARF showed overall better improvement in memory loss than donepezil, and the effect lasted for at least 1 week after termination of administration of the formula. ARF increased expression of PKA/CREB/BDNF and synaptic proteins PSD95 expression, as well as enhanced Ser9 phosphorylation of GSK3β, thus reduced p Tau in the hippocampus. Blockade of PKA signaling blunted the anti-AD-like effect of ARF, with reversal of CREB/BDNF signaling. Transcriptomic analysis indicated some changes of novel molecules along this pathway may be part of the pathological and therapeutic mechanism, which warrants further investigation. CONCLUSION ARF may display some advantageous features in treating AD with early onset, via multi-targeted manner including enhancement of neural plasticity and reduction in Tau toxicity.
基金Supported by Project of Science and Technology Department of Hebei Province(08820412D)Project of Qinghuangdao Municipal Science and Technology Bureau[QKJ(2013)No.30-35]+1 种基金Project of Shijiazhuang Municipal Science and Technology Bureau(07150193A)Scientific Research Innovation Team of Hebei Normal University of Science and Technology(TD201201)
文摘[ Objective] A histological study was conducted to investigate the toxicity of "Baikening" and the toxic effect of "Baikening" on roosters after longer- term administration at different dose levels. [ Method] Thirty 21-day-old Hy-Line Brown roosters were administered with 0.5 and 1.0 ml of "Balkening" aqueous extract through drinking water once a day for continuous 14 d. Roosters in control group and experimental groups after drug administration for 14 d and drug with- dmwal for 7 d were euthatfized; livers, kidneys, thymuses, spleens and bursas of Fabricius were collected and weighed for comparative analysis. Various tissues were prepared into paraffin-embedded slices and stained by H. E. , to observe histological changes of various organs under an optical microscope. [ Result ] After drug administration for 14 d, all the roosters in experimental groups survived; there was no visible pathological change in various organs of Hy-Line Brown roosters in each group; organ weights of Fly-Line Brown roosters in various groups showed no significant difference; observation results of tissue slices indicated that there was no pathological change in fine structures, nuclei and cytoplasm of various organs of Hy-Line Brown roosters in different groups ; various blood vessels in different organs also presented no change in blood circulation or other pathological changes. [ Conclusion] "Baikening" aqueous extract (oral administration) has no toxic and side effect on roosters in the subacute toxicity experiment.
基金supported by grants from the National Key R&D Program of China(Nos.2021YFA1101300,2021YFA1101800,and 2020YFA0112503)Strategic Priority Research Program of the Chinese Academy of Science(XDA16010303,China)+3 种基金National Natural Science Foundation of China(Nos.82101228,82030029,81970882,and 92149304)Science and Technology Department of Sichuan Province(No.2021YFS0371,China)Shenzhen Science and Technology Program(JCYJ20190814093401920 and JCYJ20210324125608022,China)Open Research Fund of State Key Laboratory of Genetic Engineering,Fudan University(No.SKLGE-2104,China).
文摘According to the World Health Organization’s world report on hearing,nearly 2.5 billion people worldwide will suffer from hearing loss by 2050,which may contribute to a severe impact on individual life quality and national economies.Sensorineural hearing loss(SNHL)occurs commonly as a result of noise exposure,aging,and ototoxic drugs,and is pathologically characterized by the impairment of mechanosensory hair cells of the inner ear,which is mainly triggered by reactive oxygen species accumulation,inflammation,and mitochondrial dysfunction.Though recent advances have been made in understanding the ability of cochlear repair and regeneration,there are still no effective therapeutic drugs for SNHL.Chinese herbal medicine which is widely distributed and easily accessible in China has demonstrated a unique curative effect against SNHL with higher safety and lower cost compared with Western medicine.Herein we present trends in research for Chinese herbal medicine for the treatment of SNHL,and elucidate their molecular mechanisms of action,to pave the way for further research and development of novel effective drugs in this field.
文摘Background:Globally,80%people use plant-derived products for treating or preventing diseases.One prevalent perception about medicinal plants is that they are safe and devoid of adverse effects.However,approximately 1,50,000 plants contain toxic substances.Objective:The present review focuses on medicinal plant extracts/fractions toxicity assessments made in preclin-ical models by oral route.Methods:Detail studies were searched from databases including PubMed and Google Scholar.A manual reference screening of the selected studies was done to identify relevant articles,with no language restriction being imposed at the time of searching.Results:The studies included were performed in rodents,and the test substances were administered orally.Our search revealed 33 widely used plants or products with significant toxicity,and phytochemicals from these plants have been summarized.Through a systematic review,we identified a plethora of medicinal plant extracts reporting safety and toxicity concerns.Conclusion:In the future,preclinical toxicokinetic studies of herbs and the determination of their no-observed-adverse-effect levels are required for a complete safety assessment.Finally,the interaction of herbs with com-monly used/over-the-counter drugs in terms of the latter’s metabolic profile should be undertaken.
基金The authors gratefully acknowledge the support of this work by the National Natural Science Foundation of China(No.81430094,81173568,81373985).
文摘Objective:This paper discusses the composition of prescription qualitative,quantitative design principles and methods based on herbal property combination,describing the method application in new prescription design.Method:Qualitative property-combination pattern(PP)calculation was based on bipartite graphing and performing a greedy algorithm which was designed to optimize obtaining a new herbal prescription.Quantitative PP calculation was based on the qualitative computation.To calculate the Euclidean distance for the PP of the new prescription,an optimized algorithm for solving the unknown minimum Euclidean distance was used with,the new weighted proportions.Finally,non-linear optimization software was used to find the minimum Euclidean distance.Results:Using the PP of classic prescription Large Yin-Nourishing Pill,applying quantitative PP calculation a new prescription was created.Mathematical algorithms based on property combinations of traditional Chinese herbs can be applied to identify compatibility and synergies of herbs within prescriptions,especially classic formulas.Conclusion:In silico methods can then be used to create new prescriptions or modify existing ones depending on need.This type of automated approach may increase efficiency in designing new drugs based on Chinese herbs.
基金financially supported by the National Key Technologies R and D Program of China(No.2015ZX09501-004-001-008)by the Industry Research Program of Traditional Chinese Medicine(No.201507004-04)
文摘The safety issue on herbal and traditional medicines(H&TM) is one of the most challenging problems and serious concern worldwide. With scientific endeavor and further exploration, we came to realize that there are great differences between H&TM and synthetic drugs in many aspects, such as medical theory, medication experience, compatibility, processing, toxicological characteristics, and safety evaluating requirements. In the current preclinical models for synthetic drugs, the safety assessment results of some conventional deemed 'nontoxic' H&TM were not well consistent with clinical situations, which resulted in major difficulties to understand the mechanisms and guide the safe and rational uses of these H&TM. Thus, based on the traditional Chinese medicine toxicity theory called You Gu Wu Yun, this paper introduces a novel safety assessment strategy for H&TM, named as disease-based toxicology. It aims to cognize the relativity and susceptibility of the toxicity of H&TM, and then to enhance controllability in new drug development and clinical applications. It also provides a theoretical practice for the traditional Chinese medicine toxicity theory and a methodological promotion for the future development of the precision toxicology for H&TM.
基金Supported by a grant to Korean Medical Science Research Center for Healthy Aging from the National Research Foundation of Korean government(No.2014R1A5A2009936)
文摘Objective: To obtain fundamental information for the standardization of herbal medicine in Korea. Methods: We analyzed the herbal medicine prescription data of patients at the Pusan National University Korean Medicine Hospital from March 2010 to February 2013. We used the Dongui-Bogam (Dong Yi Bao Jian) to classify prescribed herbal medicines. Results: The study revealed that the most frequently prescribed herbal medicine was ‘Liuwei Dihuang Pill (LWDHP, 六味地黄丸)' which was used for invigorating ‘Shen (Kidndy)-yin'. ‘LWDHP' was most frequently prescribed to male patients aged 50-59, 60-69, 70-79 and 80-89 years, and ‘Xionggui Tiaoxue Decoction (XGTXD, 芎归调血饮)' was most frequently prescribed to female patients aged 30-39 and 40-49 years. According to the International Classification of Diseases (ICD) codes,‘Diseases of the musculoskeletal system and connective tissue' showed the highest prevalence. ‘LWDHP' and 'XGTXD' was the most frequently prescribed in categories 5 and 3, respectively. Based on the percentage of prescriptions for each sex, ‘Ziyin Jianghuo Decoction (滋阴降火汤)' was prescribed to mainly male patients, and ‘XGTXD' with ‘Guima Geban Decoction (桂麻各半汤)' were prescribed to mainly female patients. Conclusion: This study analysis successfully determined the frequency of a variety of herbal medicines, and many restorative herbal medicines were identified and frequently administered.