| 1 | Emodin alleviates cardiac fibrosis by suppressing activation of cardiac fibroblasts via upregulating metastasis associated protein 3显示文摘Excess activation of cardiac fibroblasts inevitably induces cardiac fibrosis. Emodin has been used as a natural medicine against several chronic diseases. The objective of this study is to determine the effects of emodin on cardiac fibrosis and the underlying molecular mechanisms. Intragastric administration of emodin markedly decreased left ventricular wall thickness in a mouse model of pathological cardiac hypertrophy with excess fibrosis induced by transaortic constriction(TAC) and suppressed activation of cardiac fibroblasts induced by angiotensin II(AngII). Emodin upregulated expression of metastasis associated protein 3(MTA3) and restored the MTA3 expression in the setting of cardiac fibrosis. Moreover, overexpression of MTA3 promoted cardiac fibrosis;in contrast, silence of MTA3 abrogated the inhibitory effect of emodin on fibroblast activation. Our findings unraveled the potential of emodin to alleviate cardiac fibrosis via upregulating MTA3 and highlight the regulatory role of MTA3 in the development of cardiac fibrosis. | Dan Xiao Yue Zhang Rui Wang Yujie Fu Tong Zhou Hongtao Diao Zhixia Wang Yuan Lin Zhange Li Lin Wen Xujuan Kang Philipp Kopylov Dmitri Shchekochikhin Yong Zhang Baofeng Yang | 2019 | Acta Pharmaceutica Sinica B2019，9，4： | 11 |
| 2 | Nitidine chloride induces cardiac hypertrophy in mice by targeting autophagy-related 4B cysteine peptidase显示文摘Nitidine chloride(NC)is a standard active component from the traditional Chinese medicine Zanthoxylum nitidum(Roxb.)DC.(ZN).NC has shown a variety of pharmacological activities including anti-tumor activity.As a number of anti-tumor drugs cause cardiotoxicity,herein we investigated whether NC exerted a cardiotoxic effect and the underlying mechanism.Aqueous extract of ZN(ZNE)was intraperitoneally injected into rats,while NC was injected into beagles and mice once daily for 4 weeks.Cardiac function was assessed using echocardiography.We showed that both ZNE administered in rats and NC administered in mice induced dose-dependent cardiac hypertrophy and dysfunction,whereas administration of NC at the middle and high dose caused death in Beagles.Consistently,we observed a reduction of cardiac autophagy levels in NC-treated mice and neonatal mouse cardiomyocytes.Furthermore,we demonstrated that autophagy-related 4B cysteine peptidase(ATG4B)may be a potential target of NC,since overexpression of ATG4B reversed the cardiac hypertrophy and reduced autophagy levels observed in NC-treated mice.We conclude that NC induces cardiac hypertrophy via ATG4B-mediated downregulation of autophagy in mice.Thus,this study provides guidance for the safe clinical application of ZN and the use of NC as an anti-tumor drug. | Yang Hong Wan-qing Xu Jing Feng Han Lou Heng Liu Lei Wang Hao Cui Lin-tong Jiang Ran-chen Xu Heng-hui Xu Min-zhen Xie Yang Li Philipp Kopylov Qi Wang Yong Zhang | 2023 | Acta Pharmacologica Sinica2023，44，3： | 0 |
| 3 | Pharmacodynamics of frigid zone plant Taxus cuspidata S.et Z.against skin melanin deposition,oxidation,inflammation and allergy显示文摘Background:Taxus cuspidata S.et Z.is a precious species of frigid zone plant belonging to the Taxaceae family,which possesses anticancer,anti-inflammatory,hypoglycemic,and antibacterial pharmacological properties.While taxane extracted from Taxus chinensis has been reported to elicit antioxidant activities,whether Taxus cuspidata S.et Z.has skin-protective actions against injuries remained unknown.This study aims to explore the pharmacological effects of three Taxus extracts on skin melanin deposition,oxidation,inflammation,and allergy so as to provide new ideas for the prevention and treatment of various diseases related to skin damage.Methods:Skin melanin deposition was evaluated by measuring melanin content in the skin of guinea pigs by alkali lysis method.Antioxidant capacity was evaluated by measuring superoxide dismutase(SOD)concentration and glutathione(GSH)content in skin tissue homogenates of Kunming mice by SOD assay kit and micro reduced GSH assay kit.The quantitative real-time polymerase chain reaction(qRT-PCR)and western blotting were used to examine the levels of both SOD and recombinant glutathione peroxidase 4(GPX4).Skin inflammation was evaluated by xylene-induced ear swelling test and egg-white-induced paw swelling test in mice.In a mouse model of skin allergy induced by 4-aminopyridine(4-AP),allergy was determined by licking body counts and histamine concentrations in tissue homogenates using enzyme-linked immunosorbent assay(ELISA)kits.Two proinflammatory factors tumor necrosis factor(TNF)-αand interleukin(IL)-1βwere measured by qRT-PCR.Hematoxylin and eosin(HE)staining was conducted to assess the degree of skin lesion.Results:All three Taxus extracts including Taxus chinensis essential oil,Taxus chinensis extract and Taxus chinensis extract compound reduced the melanin deposits in the back skin relative to the non-treated control animals,of which Taxus chinensis essential oil produced the greatest effect.In contrast,the three Taxus extracts elevated SOD and GSH levels in the skin tissues,and the highest increase was seen with Taxus chinensis essential oil.Three Taxus extracts,especially Taxus chinensis essential oil,effectively reduce the rate of ear and paw swelling.All three Taxus extracts reduced the number of body licks,the levels of TNF-αand IL-1β,and the histamine content in tissue homogenates of mice and alleviated skin damage.Consistently,Taxus chinensis essential oil yielded the greatest magnitude of decreases.Conclusion:While all three Taxus extracts possessed the anti-skin melanin deposition,oxidation,and allergy properties,Taxus chinensis essential oil produced the superior effects. | Yang Shi Ling Liu Heyang Sun Chen Chen Jing Feng Yongchao Chen Yuan Lin Philipp Kopylov Qi Wang Yong Zhang | 2023 | Frigid Zone Medicine2023，3，1： | 0 |
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