Background: Idiosyncratic drug-induced liver injury(IDILI) is a serious side effect of drugs, Epimedii Folium(EF) is unequivocally implicated in idiosyncratic liver injury onset, potentially due to its ability to pert...Background: Idiosyncratic drug-induced liver injury(IDILI) is a serious side effect of drugs, Epimedii Folium(EF) is unequivocally implicated in idiosyncratic liver injury onset, potentially due to its ability to perturb the NOD-like receptor family pyrin domain containing 3(NLRP3) inflammasome. Fructus Ligustri Lucidi(FLL), a frequently used medicinal combination with EF, has not yet been investigated for its ability to ameliorate EF-associated hepatotoxicity. Aims and Objectives: Study on the mechanism of compatibility of FLL to alleviate liver injury caused by EF. Materials and Methods: Western blot was used to determine the expression of related proteins, ELISA was used to detect the secretion of related inflammatory factors IL-1β, IL-18, IL-6 and TNF-α, liver injury indexes were detected and liver pathological tissue staining was used to evaluate the liver injury. Results: Our results demonstrated that EF exerted a particular augmenting effect on the stimulation of the NLRP3 inflammasome mediated by nigericin or ATP, whereas FLL suppressed the NLRP3 inflammasome stimulation. Furthermore, an equal EF to FLL ratio significantly reduced the stimulatory effects of EF. Moreover, EF has the potential to induce hepatic injury and augment pro-inflammatory cytokine synthesis in rats subjected to LPS. However, when combined with FLL, the detrimental effects of EF were mitigated. Conclusions: FLL possesses the capacity to attenuate EF-associated hepatotoxicity by suppressing EF-triggered NLRP3 inflammasome activation. Thus, FLL holds promise for improving the clinical safety profile of EF, shedding light on the potential of compatibility and detoxification theories in traditional Chinese medicine.展开更多
Objective: To comparatively analyze the difference in the expression of 54 transcription factors in the hypothalamus using protein chips following the medication of Chinese drugs for Shen (肾)-tonification, Herba E...Objective: To comparatively analyze the difference in the expression of 54 transcription factors in the hypothalamus using protein chips following the medication of Chinese drugs for Shen (肾)-tonification, Herba Epimedii, and Fructus Ligustri lucidi (FL) to aged rats. Methods: Wistar rats, aged 15 months of SPF grade, were randomized into three groups, three males and three females in each group. They were medicated with Herba Epimedii decoction (HED, 0.14 g/kg), Fructus Ligustri lucidi decoction (FLD, 0.12 g/kg), and distilled water, respectively, twice a day for 15 days. The rats were sacrificed at the morning of the 16th day 1 h after medication, and their hypothalamus was taken and made into homogenate under an ice-bath for detecting the expression of transcription factors with chip technique. Results: The expressions of signal transduction and transcription activation factor-6 (Stat-6) and androgen receptor (AR) were up-regulated, and those of pre-B transcription factor1 (Pbx-1), stat-1 and AP-2 were down-regulated in both HED and FLD treated groups, but these changes occurred mainly in female rats in the former while mainly in males in the latter. Conclusions: Chinese drugs for Shen-tonification could impact the expression of transcription factors in the hypothalamus of aged rats, dominantly on the neuro-endocrine factors responsible for the growth and development. The effects of drugs for tonifying Shen-yang and for tonifying Shen-yin are different, which is probably one of the pharmacological mechanisms of the Shen-tonifying drugs.展开更多
The Chinese herbs Herba Epimedii, Fructus Ligustri Lucidi and Rhizoma Polygonati were injected into Parkinson's disease mice established via intraperitoneal injection of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridin...The Chinese herbs Herba Epimedii, Fructus Ligustri Lucidi and Rhizoma Polygonati were injected into Parkinson's disease mice established via intraperitoneal injection of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride. The selective monoamine oxidase B inhibitor selegiline was used as a positive control drug. After successive administration for 4 weeks, Herba Epimedii could downregulate the expression of caspase-3 and increase the brain-derived neurotrophic factor level, as well as increase tyrosine hydroxylase activity in the substantia nigra of Parkinson's disease mouse models. Rhizoma Polygonaticould downregulate the expression of caspase-3 and FasL, and increase neural growth factor and brain-derived neurotrophic factor levels. Fructus Ligustn Lucidi could downregulate caspase-3 expression. Rhizoma Polygonati and Fructus Ligustn Lucidi did not produce obvious effects on tyrosine hydroxylase activity. Herba Epimedii and Fructus Ligustri Lucidi yielded similar effects on apoptosis-promoting factors to those elicited by selegiline. Herba Epimedii and Rhizoma Polygonati significantly increased the levels of neurotrophic factors compared with selegiline. Herba Epimedii significantly increased tyrosine hydroxylase activity compared with selegiline. It is indicated that the kidney-tonifying Chinese herbal preparation can downregulate the expression of apoptosis-promoting factors, increase neurotrophic factors levels in the substantia nigra and striatum, as well as increase tyrosine hydroxylase activity in the substantia nigra of Parkinson's disease mouse models, thereby exerting a stronger or similar neuroprotective effects compared with selegiline.展开更多
基金supported by the State Key Program of National Natural Science of China (81930110)Military Logistics Research Project on Health Special Project (23BJZ33)the Key Project at Central Government Level: The ability establishment of sustainable use for valuable Chinese medicine resources (2060302)。
文摘Background: Idiosyncratic drug-induced liver injury(IDILI) is a serious side effect of drugs, Epimedii Folium(EF) is unequivocally implicated in idiosyncratic liver injury onset, potentially due to its ability to perturb the NOD-like receptor family pyrin domain containing 3(NLRP3) inflammasome. Fructus Ligustri Lucidi(FLL), a frequently used medicinal combination with EF, has not yet been investigated for its ability to ameliorate EF-associated hepatotoxicity. Aims and Objectives: Study on the mechanism of compatibility of FLL to alleviate liver injury caused by EF. Materials and Methods: Western blot was used to determine the expression of related proteins, ELISA was used to detect the secretion of related inflammatory factors IL-1β, IL-18, IL-6 and TNF-α, liver injury indexes were detected and liver pathological tissue staining was used to evaluate the liver injury. Results: Our results demonstrated that EF exerted a particular augmenting effect on the stimulation of the NLRP3 inflammasome mediated by nigericin or ATP, whereas FLL suppressed the NLRP3 inflammasome stimulation. Furthermore, an equal EF to FLL ratio significantly reduced the stimulatory effects of EF. Moreover, EF has the potential to induce hepatic injury and augment pro-inflammatory cytokine synthesis in rats subjected to LPS. However, when combined with FLL, the detrimental effects of EF were mitigated. Conclusions: FLL possesses the capacity to attenuate EF-associated hepatotoxicity by suppressing EF-triggered NLRP3 inflammasome activation. Thus, FLL holds promise for improving the clinical safety profile of EF, shedding light on the potential of compatibility and detoxification theories in traditional Chinese medicine.
基金Supported by the National Natural Science Foundation of China (No.30672729)CHEN Ke-ji Development Fund of Integrative Medicine(No.CKJ2010025)
文摘Objective: To comparatively analyze the difference in the expression of 54 transcription factors in the hypothalamus using protein chips following the medication of Chinese drugs for Shen (肾)-tonification, Herba Epimedii, and Fructus Ligustri lucidi (FL) to aged rats. Methods: Wistar rats, aged 15 months of SPF grade, were randomized into three groups, three males and three females in each group. They were medicated with Herba Epimedii decoction (HED, 0.14 g/kg), Fructus Ligustri lucidi decoction (FLD, 0.12 g/kg), and distilled water, respectively, twice a day for 15 days. The rats were sacrificed at the morning of the 16th day 1 h after medication, and their hypothalamus was taken and made into homogenate under an ice-bath for detecting the expression of transcription factors with chip technique. Results: The expressions of signal transduction and transcription activation factor-6 (Stat-6) and androgen receptor (AR) were up-regulated, and those of pre-B transcription factor1 (Pbx-1), stat-1 and AP-2 were down-regulated in both HED and FLD treated groups, but these changes occurred mainly in female rats in the former while mainly in males in the latter. Conclusions: Chinese drugs for Shen-tonification could impact the expression of transcription factors in the hypothalamus of aged rats, dominantly on the neuro-endocrine factors responsible for the growth and development. The effects of drugs for tonifying Shen-yang and for tonifying Shen-yin are different, which is probably one of the pharmacological mechanisms of the Shen-tonifying drugs.
基金supported by the Natural Science Foundation of Fujian Province, No. 2009J06018
文摘The Chinese herbs Herba Epimedii, Fructus Ligustri Lucidi and Rhizoma Polygonati were injected into Parkinson's disease mice established via intraperitoneal injection of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride. The selective monoamine oxidase B inhibitor selegiline was used as a positive control drug. After successive administration for 4 weeks, Herba Epimedii could downregulate the expression of caspase-3 and increase the brain-derived neurotrophic factor level, as well as increase tyrosine hydroxylase activity in the substantia nigra of Parkinson's disease mouse models. Rhizoma Polygonaticould downregulate the expression of caspase-3 and FasL, and increase neural growth factor and brain-derived neurotrophic factor levels. Fructus Ligustn Lucidi could downregulate caspase-3 expression. Rhizoma Polygonati and Fructus Ligustn Lucidi did not produce obvious effects on tyrosine hydroxylase activity. Herba Epimedii and Fructus Ligustri Lucidi yielded similar effects on apoptosis-promoting factors to those elicited by selegiline. Herba Epimedii and Rhizoma Polygonati significantly increased the levels of neurotrophic factors compared with selegiline. Herba Epimedii significantly increased tyrosine hydroxylase activity compared with selegiline. It is indicated that the kidney-tonifying Chinese herbal preparation can downregulate the expression of apoptosis-promoting factors, increase neurotrophic factors levels in the substantia nigra and striatum, as well as increase tyrosine hydroxylase activity in the substantia nigra of Parkinson's disease mouse models, thereby exerting a stronger or similar neuroprotective effects compared with selegiline.