Depression is a highly heterogeneous mental illness. Drug treatment is currently the main therapeutic strategy used in the clinic, but its efficacy is limited by the modulation of a single target, slow onset, and side effects. The gut-brain axis is of increasing interest because intestinal microenvironment disorders increase susceptibility to depression. In turn, depression affects intestinal microenvironment homeostasis by altering intestinal tissue structure, flora abundance and metabolism, hormone secretion, neurotransmitter transmission, and immune balance. Depression falls into the category of "stagnation syndrome" according to Traditional Chinese Medicine (TCM), which further specifies that "the heart governs the spirit and is exterior-interior with the small intestine". However, the exact mechanisms of the means by which the disordered intestinal microenvironment affects depression are still unclear. Here, we present an overview of how the Chinese materia medica (CMM) protects against depression by repairing intestinal microenvironment homeostasis. We review the past five years of research progress in classical antidepressant TCM formulae and single CMMs on regulating the intestinal microenvironment for the treatment of depression. We then analyze and clarify the multitarget functions of CMM in repairing intestinal homeostasis and aim to provide a new theoretical basis for CMM clinical application in the treatment of depression.
{"title":"Chinese Materia Medica in Treating Depression: The Role of Intestinal Microenvironment.","authors":"Ruhui Shen, Zhipeng Li, Huiyun Wang, Yongchao Wang, Xiaofang Li, Qian Yang, Yingjie Fu, Ming Li, Li-Na Gao","doi":"10.1142/S0192415X23500854","DOIUrl":"10.1142/S0192415X23500854","url":null,"abstract":"<p><p>Depression is a highly heterogeneous mental illness. Drug treatment is currently the main therapeutic strategy used in the clinic, but its efficacy is limited by the modulation of a single target, slow onset, and side effects. The gut-brain axis is of increasing interest because intestinal microenvironment disorders increase susceptibility to depression. In turn, depression affects intestinal microenvironment homeostasis by altering intestinal tissue structure, flora abundance and metabolism, hormone secretion, neurotransmitter transmission, and immune balance. Depression falls into the category of \"stagnation syndrome\" according to Traditional Chinese Medicine (TCM), which further specifies that \"the heart governs the spirit and is exterior-interior with the small intestine\". However, the exact mechanisms of the means by which the disordered intestinal microenvironment affects depression are still unclear. Here, we present an overview of how the Chinese materia medica (CMM) protects against depression by repairing intestinal microenvironment homeostasis. We review the past five years of research progress in classical antidepressant TCM formulae and single CMMs on regulating the intestinal microenvironment for the treatment of depression. We then analyze and clarify the multitarget functions of CMM in repairing intestinal homeostasis and aim to provide a new theoretical basis for CMM clinical application in the treatment of depression.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71490769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emodin is a natural compound found in several traditional Chinese medicines, including Rheum palmatum and Polygonum cuspidatum. Recent studies have shown that emodin exhibits potent anticancer effects against a variety of cancer types, including liver, breast, lung, and colon cancer. Emodin's anticancer effects are mediated through several mechanisms, including inhibition of cell proliferation, induction of apoptosis, and suppression of tumor angiogenesis and metastasis. In this review, we provide an overview of recent research progress and new perspectives on emodin's anticancer effect. We summarize the current understanding of the molecular mechanisms underlying emodin's anticancer activity, including its effects on signaling pathways such as the PI3K/Akt, MAPK, and NF-[Formula: see text]B pathways. We also discuss the potential of emodin as a therapeutic agent for cancer treatment, including its use in combination with conventional chemotherapeutic drugs and as a sensitizer for radiotherapy. Furthermore, we highlight recent advances in the development of emodin derivatives and their potential as novel anticancer agents. Finally, we discuss the challenges and opportunities for the translation of emodin's anticancer properties into clinical applications, including the need for further preclinical and clinical studies to evaluate its safety and efficacy. In conclusion, emodin represents a promising natural compound with potent anticancer properties, and its potential as a therapeutic agent for cancer treatment warrants further investigation. This review provides a comprehensive overview of the current research progress and new perspectives on emodin's anticancer effects, which may facilitate the development of novel therapeutic strategies for cancer treatment.
{"title":"Research Progress and New Perspectives of Anticancer Effects of Emodin.","authors":"Wu Liu, Eskandar Qaed, Yuelin Zhu, Wenzhang Tian, Yizhen Wang, Le Kang, Xiaodong Ma, Zeyao Tang","doi":"10.1142/S0192415X23500787","DOIUrl":"10.1142/S0192415X23500787","url":null,"abstract":"<p><p>Emodin is a natural compound found in several traditional Chinese medicines, including <i>Rheum palmatum</i> and <i>Polygonum cuspidatum</i>. Recent studies have shown that emodin exhibits potent anticancer effects against a variety of cancer types, including liver, breast, lung, and colon cancer. Emodin's anticancer effects are mediated through several mechanisms, including inhibition of cell proliferation, induction of apoptosis, and suppression of tumor angiogenesis and metastasis. In this review, we provide an overview of recent research progress and new perspectives on emodin's anticancer effect. We summarize the current understanding of the molecular mechanisms underlying emodin's anticancer activity, including its effects on signaling pathways such as the PI3K/Akt, MAPK, and NF-[Formula: see text]B pathways. We also discuss the potential of emodin as a therapeutic agent for cancer treatment, including its use in combination with conventional chemotherapeutic drugs and as a sensitizer for radiotherapy. Furthermore, we highlight recent advances in the development of emodin derivatives and their potential as novel anticancer agents. Finally, we discuss the challenges and opportunities for the translation of emodin's anticancer properties into clinical applications, including the need for further preclinical and clinical studies to evaluate its safety and efficacy. In conclusion, emodin represents a promising natural compound with potent anticancer properties, and its potential as a therapeutic agent for cancer treatment warrants further investigation. This review provides a comprehensive overview of the current research progress and new perspectives on emodin's anticancer effects, which may facilitate the development of novel therapeutic strategies for cancer treatment.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41109731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andrographolide (AND) is a bioactive component of the herb Andrographis paniculata and a well-known anti-inflammatory agent. Atherosclerosis is a chronic inflammatory disease of the vasculature, and oxidized LDL (oxLDL) is thought to contribute heavily to atherosclerosis-associated inflammation. The aim of this study was to investigate whether AND mitigates oxLDL-mediated foam cell formation and diet-induced atherosclerosis (in mice fed a high-fat, high-cholesterol, high-cholic acid [HFCCD] diet) and the underlying mechanisms involved. AND attenuated LPS/oxLDL-mediated foam cell formation, IL-1[Formula: see text] mRNA and protein (p37) expression, NLR family pyrin domain containing 3 (NLRP3) mRNA and protein expression, caspase-1 (p20) protein expression, and IL-1[Formula: see text] release in BMDMs. Treatment with oxLDL significantly induced protein and mRNA expression of CD36, lectin-like oxLDL receptor-1 (LOX-1), and scavenger receptor type A (SR-A), whereas pretreatment with AND significantly inhibited protein and mRNA expression of SR-A only. Treatment with oxLDL significantly induced ROS generation and Dil-oxLDL uptake; however, pretreatment with AND alleviated oxLDL-induced ROS generation and Dil-oxLDL uptake. HFCCD feeding significantly increased aortic lipid accumulation, ICAM-1 expression, and IL-1[Formula: see text] mRNA expression, as well as blood levels of glutamic pyruvic transaminase (GPT), total cholesterol, and LDL-C. AND co-administration mitigated aortic lipid accumulation, the protein expression of ICAM-1, mRNA expression of IL-1[Formula: see text] and ICAM-1, and blood levels of GPT. These results suggest that the working mechanisms by which AND mitigates atherosclerosis involve the inhibition of foam cell formation and NLRP3 inflammasome-dependent vascular inflammation as evidenced by decreased SR-A expression and IL-1[Formula: see text] release, respectively.
{"title":"Andrographolide Attenuates Oxidized LDL-Induced Activation of the NLRP3 Inflammasome in Bone Marrow-Derived Macrophages and Mitigates HFCCD-Induced Atherosclerosis in Mice.","authors":"Chih-Chieh Chen, Chong-Kuei Lii, Kai-Li Liu, Yi-Ling Lin, Chia-Wen Lo, Chien-Chun Li, Ya-Chen Yang, Haw-Wen Chen","doi":"10.1142/S0192415X23500933","DOIUrl":"10.1142/S0192415X23500933","url":null,"abstract":"<p><p>Andrographolide (AND) is a bioactive component of the herb <i>Andrographis paniculata</i> and a well-known anti-inflammatory agent. Atherosclerosis is a chronic inflammatory disease of the vasculature, and oxidized LDL (oxLDL) is thought to contribute heavily to atherosclerosis-associated inflammation. The aim of this study was to investigate whether AND mitigates oxLDL-mediated foam cell formation and diet-induced atherosclerosis (in mice fed a high-fat, high-cholesterol, high-cholic acid [HFCCD] diet) and the underlying mechanisms involved. AND attenuated LPS/oxLDL-mediated foam cell formation, IL-1[Formula: see text] mRNA and protein (p37) expression, NLR family pyrin domain containing 3 (NLRP3) mRNA and protein expression, caspase-1 (p20) protein expression, and IL-1[Formula: see text] release in BMDMs. Treatment with oxLDL significantly induced protein and mRNA expression of CD36, lectin-like oxLDL receptor-1 (LOX-1), and scavenger receptor type A (SR-A), whereas pretreatment with AND significantly inhibited protein and mRNA expression of SR-A only. Treatment with oxLDL significantly induced ROS generation and Dil-oxLDL uptake; however, pretreatment with AND alleviated oxLDL-induced ROS generation and Dil-oxLDL uptake. HFCCD feeding significantly increased aortic lipid accumulation, ICAM-1 expression, and IL-1[Formula: see text] mRNA expression, as well as blood levels of glutamic pyruvic transaminase (GPT), total cholesterol, and LDL-C. AND co-administration mitigated aortic lipid accumulation, the protein expression of ICAM-1, mRNA expression of IL-1[Formula: see text] and ICAM-1, and blood levels of GPT. These results suggest that the working mechanisms by which AND mitigates atherosclerosis involve the inhibition of foam cell formation and NLRP3 inflammasome-dependent vascular inflammation as evidenced by decreased SR-A expression and IL-1[Formula: see text] release, respectively.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71490768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01Epub Date: 2023-11-10DOI: 10.1142/S0192415X2350088X
Shuran Zhang, Junyu He, Jie Li, Haibo He, Yumin He, Xiao Wang, Heng Shu, Jihong Zhang, Daoxiang Xu, Kun Zou
Cyclocarya paliurus (Batalin) Iljinskaja (C. paliurus) is a single species of Cyclocarya paliurus in Juglandaceae. It is a unique rare medicinal plant resource in China that is mainly distributed in the south of China. The leaves of C. paliurus, as a new food ingredient, are processed into tea products in daily life. Triterpenoids are the main active ingredient in C. paliurus. So far, 164 triterpenoid compounds have been isolated and identified from C. paliurus, which are included 3,4-seco-dammaranes, dammaranes, oleanane, ursane, lupinanes, taraxeranes, and norceanothanes. Modern pharmacological studies manifested that these ingredients have a wide range of pharmacological activities both in vitro and in vivo, such as reducing blood sugar, lowering blood lipids, and anti-tumor, anti-inflammatory, anti-oxidant, and other activities. In addition, current results indicate that the pharmacological mechanisms of triterpenoids were closely related to their chemical structure, molecular signaling pathways, and the expression of related proteins. In order to further study C. paliurus based on the current research situation, this review summarizes the prospect and systematic summary of the triterpenes of C. paliurus from the aspects of structural characteristics, quality control, biological activity, and the structure-activity relationship, which provide a reference for further research and application of the triterpenoids from C. paliurus in the field of functional food and medicine.
{"title":"Triterpenoid Compounds from <i>Cyclocarya paliurus</i>: A Review of Their Phytochemistry, Quality Control, Pharmacology, and Structure-Activity Relationship.","authors":"Shuran Zhang, Junyu He, Jie Li, Haibo He, Yumin He, Xiao Wang, Heng Shu, Jihong Zhang, Daoxiang Xu, Kun Zou","doi":"10.1142/S0192415X2350088X","DOIUrl":"10.1142/S0192415X2350088X","url":null,"abstract":"<p><p><i>Cyclocarya paliurus</i> (Batalin) Iljinskaja (<i>C. paliurus</i>) is a single species of <i>Cyclocarya paliurus</i> in Juglandaceae. It is a unique rare medicinal plant resource in China that is mainly distributed in the south of China. The leaves of <i>C. paliurus</i>, as a new food ingredient, are processed into tea products in daily life. Triterpenoids are the main active ingredient in <i>C. paliurus</i>. So far, 164 triterpenoid compounds have been isolated and identified from <i>C. paliurus</i>, which are included 3,4-seco-dammaranes, dammaranes, oleanane, ursane, lupinanes, taraxeranes, and norceanothanes. Modern pharmacological studies manifested that these ingredients have a wide range of pharmacological activities both <i>in vitro</i> and <i>in vivo</i>, such as reducing blood sugar, lowering blood lipids, and anti-tumor, anti-inflammatory, anti-oxidant, and other activities. In addition, current results indicate that the pharmacological mechanisms of triterpenoids were closely related to their chemical structure, molecular signaling pathways, and the expression of related proteins. In order to further study <i>C. paliurus</i> based on the current research situation, this review summarizes the prospect and systematic summary of the triterpenes of <i>C. paliurus</i> from the aspects of structural characteristics, quality control, biological activity, and the structure-activity relationship, which provide a reference for further research and application of the triterpenoids from <i>C. paliurus</i> in the field of functional food and medicine.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92158166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuangeng Li, Ping Yu, Wenwen Fu, Shuo Wang, Wenjun Zhao, Yue Ma, Yi Wu, Heming Cui, Xiaofeng Yu, L. Fu, Huali Xu, Dayun Sui
Carbon tetrachloride (CCl4)-induced lipid peroxidation associated with hepatic oxidative stress and cell death is an important mechanism of acute liver injury (ALI). Ginsenoside Rd is considered an active ingredient of ginseng. Evidence suggests that ginsenoside Rd may improve ischaemic stroke, nerve damage, cancer and other diseases involving apoptosis, inflammation, oxidative stress, mitochondrial injury and autophagy. However, the effects of ginsenoside Rd on CCl4-induced ALI and its underlying mechanisms are still unclear. In this study, 0.25% CCl4 was injected intraperitoneally in mice to establish a CCl4-induced ALI model. In the Rd treatment group, Rd (10, 20[Formula: see text]mg/kg) doses were injected intraperitoneally 1[Formula: see text]h before and 23[Formula: see text]h after CCl4 administration. Ferroptosis inducer imidazole ketone erastin (IKE) was injected intraperitoneally 4[Formula: see text]h before CCl4 administration to explore the mechanism. The blood and liver were collected 24[Formula: see text]h after CCl4 administration to investigate the effect and mechanism of ginsenoside Rd on CCl4-induced ALI. Our results showed that ginsenoside Rd inhibited CCl4-induced ALI in mice. Ginsenoside Rd also downregulated CCl4-induced serum and liver iron, 4-hydroxynonenal, and 8-hydroxy-2 deoxyguanosine levels. Furthermore, it upregulated glutathione and glutathione peroxidase 4 levels. In addition, ginsenoside Rd downregulated the expression of cGAS and STING. Subsequently, the ferroptosis inducer imidazole ketone erastin significantly reversed the hepatoprotective effect and influence of ginsenoside Rd with regard to the indicators mentioned above. Our study confirmed that ginsenoside Rd ameliorated CCl4-induced ALI in mice, which was related to the reduction of ferroptosis. Simultaneously, the ginsenoside Rd-mediated inhibition of the cGAS/STING pathway contributed to its antiferroptosis effect. In conclusion, our results suggested that ginsenoside Rd inhibited ferroptosis via the cGAS/STING pathway, thereby protecting mice from CCl4-induced ALI. These results suggested ginsenoside Rd may be used as a potential intervention treatment against CCl4-induced ALI.
{"title":"Ginsenoside Rd Inhibited Ferroptosis to Alleviate CCl4-Induced Acute Liver Injury in Mice via cGAS/STING Pathway.","authors":"Yuangeng Li, Ping Yu, Wenwen Fu, Shuo Wang, Wenjun Zhao, Yue Ma, Yi Wu, Heming Cui, Xiaofeng Yu, L. Fu, Huali Xu, Dayun Sui","doi":"10.2139/ssrn.4100254","DOIUrl":"https://doi.org/10.2139/ssrn.4100254","url":null,"abstract":"Carbon tetrachloride (CCl4)-induced lipid peroxidation associated with hepatic oxidative stress and cell death is an important mechanism of acute liver injury (ALI). Ginsenoside Rd is considered an active ingredient of ginseng. Evidence suggests that ginsenoside Rd may improve ischaemic stroke, nerve damage, cancer and other diseases involving apoptosis, inflammation, oxidative stress, mitochondrial injury and autophagy. However, the effects of ginsenoside Rd on CCl4-induced ALI and its underlying mechanisms are still unclear. In this study, 0.25% CCl4 was injected intraperitoneally in mice to establish a CCl4-induced ALI model. In the Rd treatment group, Rd (10, 20[Formula: see text]mg/kg) doses were injected intraperitoneally 1[Formula: see text]h before and 23[Formula: see text]h after CCl4 administration. Ferroptosis inducer imidazole ketone erastin (IKE) was injected intraperitoneally 4[Formula: see text]h before CCl4 administration to explore the mechanism. The blood and liver were collected 24[Formula: see text]h after CCl4 administration to investigate the effect and mechanism of ginsenoside Rd on CCl4-induced ALI. Our results showed that ginsenoside Rd inhibited CCl4-induced ALI in mice. Ginsenoside Rd also downregulated CCl4-induced serum and liver iron, 4-hydroxynonenal, and 8-hydroxy-2 deoxyguanosine levels. Furthermore, it upregulated glutathione and glutathione peroxidase 4 levels. In addition, ginsenoside Rd downregulated the expression of cGAS and STING. Subsequently, the ferroptosis inducer imidazole ketone erastin significantly reversed the hepatoprotective effect and influence of ginsenoside Rd with regard to the indicators mentioned above. Our study confirmed that ginsenoside Rd ameliorated CCl4-induced ALI in mice, which was related to the reduction of ferroptosis. Simultaneously, the ginsenoside Rd-mediated inhibition of the cGAS/STING pathway contributed to its antiferroptosis effect. In conclusion, our results suggested that ginsenoside Rd inhibited ferroptosis via the cGAS/STING pathway, thereby protecting mice from CCl4-induced ALI. These results suggested ginsenoside Rd may be used as a potential intervention treatment against CCl4-induced ALI.","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44382569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-06-08DOI: 10.1142/S0192415X22500586
Shumeng Lin, Jing Wen, Xiao Xu, Jiamin Shi, Wen Zhang, Tiansheng Zheng, Yaqin Hou, Yanfei Zhang, Zi-wei Li, Kai Wang, Jing Jin, Liduo Yue, Baigenzhin Abay, Ming Li, Qingxi Yue, L. Fan
Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death worldwide. Amygdalin, a natural compound commonly distributed in plants of the Rosaceae species, owns anticancer activity, less side effects, wide source, and relatively low price. Although the apoptosis is a central process activated by amygdalin in cancer cells, the underlying molecular mechanisms through which amygdalin induces the apoptosis of lung cancer cells remain poorly understood. In this research work, amygdalin could suppress the proliferation of lung cancer A549 and PC9 cells by CCK8 assay. Amygdalin significantly promoted the apoptosis of lung cancer A549 and PC9 cells stained with Annexin V-FITC/PI by flow cytometry assay. Furthermore, amygdalin dose-dependently decreased the mitochondrial membrane potential (MMP) with JC-1 dye by flow cytometry. To investigate the underlying molecular mechanisms through which amygdalin induced mitochondria-mediated apoptosis of cancer cells, the differentially-expressed genes with a fold change >2.0 and [Formula: see text] < 0.05 were acquired from the cDNA microarray analysis. The results of qRT-PCR further confirmed that the differentially-expressed level of the NF[Formula: see text]B-1 gene was most obviously enhanced in lung cancer cells treated with amygdalin. The results of immunofluorescence staining, Western blotting and siRNA knockdown indicated that amygdalin induced mitochondria-mediated apoptosis of lung cancer cells via enhancing the expression of NF[Formula: see text]B-1 and inactivating NF[Formula: see text]B signaling cascade and further changing the expressions of proteins (Bax, Bcl-2, cytochrome C, caspase 9, caspase 3 and PARP) related to apoptosis, which were further checked by in vivo study of the lung cancer cell xenograft mice model accompanying with immunohistochemical staining and TUNEL staining. Our results indicated that amygdalin might be a potential activator of NF[Formula: see text]B-1, which sheds more light on the molecular mechanism of anticancer effects of amygdalin. These results highlighted amygdalin as a potential therapeutic anticancer agent, which warrants its development as a therapy for lung cancer.
{"title":"Amygdalin Induced Mitochondria-Mediated Apoptosis of Lung Cancer Cells via Regulating NF[Formula: see text]B-1/NF[Formula: see text]B Signaling Cascade in Vitro and in Vivo.","authors":"Shumeng Lin, Jing Wen, Xiao Xu, Jiamin Shi, Wen Zhang, Tiansheng Zheng, Yaqin Hou, Yanfei Zhang, Zi-wei Li, Kai Wang, Jing Jin, Liduo Yue, Baigenzhin Abay, Ming Li, Qingxi Yue, L. Fan","doi":"10.1142/S0192415X22500586","DOIUrl":"https://doi.org/10.1142/S0192415X22500586","url":null,"abstract":"Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death worldwide. Amygdalin, a natural compound commonly distributed in plants of the Rosaceae species, owns anticancer activity, less side effects, wide source, and relatively low price. Although the apoptosis is a central process activated by amygdalin in cancer cells, the underlying molecular mechanisms through which amygdalin induces the apoptosis of lung cancer cells remain poorly understood. In this research work, amygdalin could suppress the proliferation of lung cancer A549 and PC9 cells by CCK8 assay. Amygdalin significantly promoted the apoptosis of lung cancer A549 and PC9 cells stained with Annexin V-FITC/PI by flow cytometry assay. Furthermore, amygdalin dose-dependently decreased the mitochondrial membrane potential (MMP) with JC-1 dye by flow cytometry. To investigate the underlying molecular mechanisms through which amygdalin induced mitochondria-mediated apoptosis of cancer cells, the differentially-expressed genes with a fold change >2.0 and [Formula: see text] < 0.05 were acquired from the cDNA microarray analysis. The results of qRT-PCR further confirmed that the differentially-expressed level of the NF[Formula: see text]B-1 gene was most obviously enhanced in lung cancer cells treated with amygdalin. The results of immunofluorescence staining, Western blotting and siRNA knockdown indicated that amygdalin induced mitochondria-mediated apoptosis of lung cancer cells via enhancing the expression of NF[Formula: see text]B-1 and inactivating NF[Formula: see text]B signaling cascade and further changing the expressions of proteins (Bax, Bcl-2, cytochrome C, caspase 9, caspase 3 and PARP) related to apoptosis, which were further checked by in vivo study of the lung cancer cell xenograft mice model accompanying with immunohistochemical staining and TUNEL staining. Our results indicated that amygdalin might be a potential activator of NF[Formula: see text]B-1, which sheds more light on the molecular mechanism of anticancer effects of amygdalin. These results highlighted amygdalin as a potential therapeutic anticancer agent, which warrants its development as a therapy for lung cancer.","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41473174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-06-08DOI: 10.1142/S0192415X22500501
Chao Ding, Yu-ze Li, Yu Sun, Ying Wu, Fengrui Wang, Chenwang Liu, Huawei Zhang, Yi Jiang, Dongdong Zhang, Xiaomei Song
Sinomenium acutumis the dry stem of Sinomenium acutum (Thunb.) Rehd et Wils. (S. acutum) and Sinomenium acutum(Thunb.) Rehd. et Wils. var. cinereumRehd. et Wils and is mainly distributed in China and Japan. As a traditional Chinese medicine (TCM) for dispelling wind and dampness in China, it is widely distributed and has a long history of drug use. In recent years, with the increase of the incidence of rheumatoid disease, S. acutum has become the focus of research. This paper reviews the literature on the chemical constituents, pharmacological effects, clinical applications and pharmacokinetics and safety of S. acutum from the past 60 years. At present, more than 210 natural compounds have been isolated from S. acutum, including alkaloids, lignans, triterpenoid saponins, steroids, and other structures. Pharmacological activities of S. acutum were mainly reported on anti-inflammatory, analgesic, anti-allergic, immunosuppressive, anti-tumor, liver-protective, anti-oxidative, and other effects, and clinical applications were mainly recorded on rheumatoid arthritis, ankylosing spondylitis, and other diseases. The clinical use of SIN has fewer side effects and more safety; only a small number of gastrointestinal reactions occurred, and the symptoms disappeared after the drug stopped. The purpose of this paper is to lay a foundation and provide reference for the follow-up research and wide application of S. acutum.
{"title":"Sinomenium acutum: A Comprehensive Review of its Botany, Phytochemistry, Pharmacology and Clinical Application.","authors":"Chao Ding, Yu-ze Li, Yu Sun, Ying Wu, Fengrui Wang, Chenwang Liu, Huawei Zhang, Yi Jiang, Dongdong Zhang, Xiaomei Song","doi":"10.1142/S0192415X22500501","DOIUrl":"https://doi.org/10.1142/S0192415X22500501","url":null,"abstract":"Sinomenium acutumis the dry stem of Sinomenium acutum (Thunb.) Rehd et Wils. (S. acutum) and Sinomenium acutum(Thunb.) Rehd. et Wils. var. cinereumRehd. et Wils and is mainly distributed in China and Japan. As a traditional Chinese medicine (TCM) for dispelling wind and dampness in China, it is widely distributed and has a long history of drug use. In recent years, with the increase of the incidence of rheumatoid disease, S. acutum has become the focus of research. This paper reviews the literature on the chemical constituents, pharmacological effects, clinical applications and pharmacokinetics and safety of S. acutum from the past 60 years. At present, more than 210 natural compounds have been isolated from S. acutum, including alkaloids, lignans, triterpenoid saponins, steroids, and other structures. Pharmacological activities of S. acutum were mainly reported on anti-inflammatory, analgesic, anti-allergic, immunosuppressive, anti-tumor, liver-protective, anti-oxidative, and other effects, and clinical applications were mainly recorded on rheumatoid arthritis, ankylosing spondylitis, and other diseases. The clinical use of SIN has fewer side effects and more safety; only a small number of gastrointestinal reactions occurred, and the symptoms disappeared after the drug stopped. The purpose of this paper is to lay a foundation and provide reference for the follow-up research and wide application of S. acutum.","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41680956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-06-04DOI: 10.1142/S0192415X22500525
Jing Li, Xuming Ma, Jun Yang, Lu Wang, Yan Huang, Yan Zhu
Cardiovascular disease is a global health problem. Previous studies revealed that it involves acute myocardial infarction and ischemia-reperfusion (I/R) injury. The mechanism of myocardial I/R injury is complex. But recognizing its mechanisms will bring important clinical significance. Lupeol is widely found in Chinese medicinal herbs and has been shown to have a variety of bio-activities. However, the pharmacological action of lupeol in the progress of myocardial ischemia-reperfusion injury (MIRI) is unclear. This study used a rat myocardial I/R model and the morphological changes in myocardium were determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining. The expression levels of IL-10, IL-1[Formula: see text], TNF-[Formula: see text], and IL-6 were assessed by quantitative real-time PCR (qRT-PCR) and ELISA. The expression levels of MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH) level and inflammatory cytokines were quantified using ELISA. The cellular apoptotic rate was determined by TUNEL staining. The findings showed that lupeol significantly decreased myocardial infarction after I/R and ameliorated I/R-induced myocardial inflammation, apoptosis, and oxidative stress. Furthermore, our results suggested that lupeol protected against MIRI-induced myocardial infarction through modulation of NF-[Formula: see text]B and Nrf2 signaling pathways. In summary, this study first clarified the cardioprotective effects of lupeol against I/R-induced myocardial infarction in rats, which could be due to its anti-oxidant, anti-inflammatory, and anti-apoptotic activities. Our study also highlighted a mechanism of NF-[Formula: see text]B and Nrf2 signaling, through which lupeol could be a promising agent in protecting against I/R-induced myocardial infarction.
{"title":"Lupeol Alleviates Myocardial Ischemia-Reperfusion Injury in Rats by Regulating NF-[Formula: see text]B and Nrf2 Pathways.","authors":"Jing Li, Xuming Ma, Jun Yang, Lu Wang, Yan Huang, Yan Zhu","doi":"10.1142/S0192415X22500525","DOIUrl":"https://doi.org/10.1142/S0192415X22500525","url":null,"abstract":"Cardiovascular disease is a global health problem. Previous studies revealed that it involves acute myocardial infarction and ischemia-reperfusion (I/R) injury. The mechanism of myocardial I/R injury is complex. But recognizing its mechanisms will bring important clinical significance. Lupeol is widely found in Chinese medicinal herbs and has been shown to have a variety of bio-activities. However, the pharmacological action of lupeol in the progress of myocardial ischemia-reperfusion injury (MIRI) is unclear. This study used a rat myocardial I/R model and the morphological changes in myocardium were determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining. The expression levels of IL-10, IL-1[Formula: see text], TNF-[Formula: see text], and IL-6 were assessed by quantitative real-time PCR (qRT-PCR) and ELISA. The expression levels of MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH) level and inflammatory cytokines were quantified using ELISA. The cellular apoptotic rate was determined by TUNEL staining. The findings showed that lupeol significantly decreased myocardial infarction after I/R and ameliorated I/R-induced myocardial inflammation, apoptosis, and oxidative stress. Furthermore, our results suggested that lupeol protected against MIRI-induced myocardial infarction through modulation of NF-[Formula: see text]B and Nrf2 signaling pathways. In summary, this study first clarified the cardioprotective effects of lupeol against I/R-induced myocardial infarction in rats, which could be due to its anti-oxidant, anti-inflammatory, and anti-apoptotic activities. Our study also highlighted a mechanism of NF-[Formula: see text]B and Nrf2 signaling, through which lupeol could be a promising agent in protecting against I/R-induced myocardial infarction.","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44741359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cisplatin is massively used to treat solid tumors. However, several severe adverse effects, such as cardiotoxicity, are obstacles to its clinical application. Cardiotoxicity may lead to congestive heart failure and even sudden cardiac death in patients receiving cisplatin. Therefore, finding a novel therapeutic strategy for the prevention of cisplatin-induced cardiotoxicity is urgent. Quercetin is a flavonol compound that can be found in dietary fruits and vegetables. The antioxidant function and anti-inflammatory capacity of quercetin have been reported. However, whether quercetin could protect against cisplatin-caused apoptosis and cellular damage in cardiomyocytes is still unclear. H9c2 cardiomyocytes were treated with cisplatin (40 [Formula: see text] M) for 24 h to induce cellular damage with or without quercetin pretreatment. We found that quercetin activates Nrf2 and HO-1 expression, thereby mitigating cisplatin-caused cytotoxicity in H9c2 cells. Quercetin also increases SOD levels, maintains mitochondrial function, and reduces oxidative stress under cisplatin stimulation. Quercetin attenuates cisplatin-induced apoptosis and inflammation in H9c2 cardiomyocytes; however, these cytoprotective effects were diminished by silencing Nrf2 and HO-1. In conclusion, this study reports that quercetin has the potential to antagonize cisplatin-caused cardiotoxicity by reducing ROS-mediated mitochondrial damage and inflammation via the Nrf2/HO-1 and p38MAPK/NF-[Formula: see text]Bp65/IL-8 signaling pathway. This study provided the theoretical basis and experimental proof for the clinical application of quercetin as a new effective strategy to relieve chemotherapy-induced cardiotoxicity.
{"title":"Quercetin Mitigates Cisplatin-Induced Oxidative Damage and Apoptosis in Cardiomyocytes through Nrf2/HO-1 Signaling Pathway.","authors":"Shih-Hao Wang, Kun-Ling Tsai, Wan-Ching Chou, Hui-Ching Cheng, Yu-Ting Huang, H. Ou, Yun-Ching Chang","doi":"10.1142/S0192415X22500537","DOIUrl":"https://doi.org/10.1142/S0192415X22500537","url":null,"abstract":"Cisplatin is massively used to treat solid tumors. However, several severe adverse effects, such as cardiotoxicity, are obstacles to its clinical application. Cardiotoxicity may lead to congestive heart failure and even sudden cardiac death in patients receiving cisplatin. Therefore, finding a novel therapeutic strategy for the prevention of cisplatin-induced cardiotoxicity is urgent. Quercetin is a flavonol compound that can be found in dietary fruits and vegetables. The antioxidant function and anti-inflammatory capacity of quercetin have been reported. However, whether quercetin could protect against cisplatin-caused apoptosis and cellular damage in cardiomyocytes is still unclear. H9c2 cardiomyocytes were treated with cisplatin (40 [Formula: see text] M) for 24 h to induce cellular damage with or without quercetin pretreatment. We found that quercetin activates Nrf2 and HO-1 expression, thereby mitigating cisplatin-caused cytotoxicity in H9c2 cells. Quercetin also increases SOD levels, maintains mitochondrial function, and reduces oxidative stress under cisplatin stimulation. Quercetin attenuates cisplatin-induced apoptosis and inflammation in H9c2 cardiomyocytes; however, these cytoprotective effects were diminished by silencing Nrf2 and HO-1. In conclusion, this study reports that quercetin has the potential to antagonize cisplatin-caused cardiotoxicity by reducing ROS-mediated mitochondrial damage and inflammation via the Nrf2/HO-1 and p38MAPK/NF-[Formula: see text]Bp65/IL-8 signaling pathway. This study provided the theoretical basis and experimental proof for the clinical application of quercetin as a new effective strategy to relieve chemotherapy-induced cardiotoxicity.","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43830800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-31DOI: 10.1142/S0192415X22500550
Liz Kong, Meng Xu, Licong Yang, Shanshan Liu, G. Zheng
The aim of this study is to investigate the molecular mechanism of Smilax china L. polyphenols (SCLPs) in enhancing lipid metabolism and stimulating browning to reduce lipid accumulation in 3T3-L1 adipocytes. SCLP treatment obviously decreased lipid content in a dose-dependent manner (10-40 [Formula: see text]g/mL) in adipocytes. SCLP treatment cooperated with noradrenalin to increase lipolysis. SCLPs reduced the gene expressions of C/EBP[Formula: see text] and Ap2and enhanced the expressions of ACO, CPT, pHSL/HSL, ATGL, and PKA in adipocytes. Furthermore, SCLPs increased mRNA and protein expressions of brown adipocyte-specific factors (UCP-1, PRDM16, PGC-1[Formula: see text], and PPAR[Formula: see text] and mRNA expressions of beige adipocyte-specific markers (CD137, Tbx1, and Tmem26) in 3T3-L1 adipocytes, as well as mitochondrial biogenesis genes (Nrf1 and Tfam). In addition, according to the immunofluorescence staining, the mitochondria number was increased by SCLP. Moreover, [Formula: see text]3-AR or AMPK agonist synergistic SCLPs enhanced the expressions of UCP-1, PRDM16, and PGC-1[Formula: see text]. While [Formula: see text]3-AR or AMPK antagonist significantly decreased the expressions of these brown adipocyte-specific factors, SCLP treatment inhibited the effect of antagonist to improve the expression of UCP-1, PRDM16, and PGC-1[Formula: see text]. These results indicated that SCLPs may regulate lipid metabolism and stimulate browning via the [Formula: see text]3-AR/AMPK[Formula: see text] signaling pathway. Thus, SCLPs likely have potential therapeutic effects on obesity.
{"title":"Smilax china Polyphenols Stimulate Browning via [Formula: see text]3-Adrenergic Receptor/AMP-Activated Protein Kinase [Formula: see text] Signaling Pathway in 3T3-L1 Adipocytes.","authors":"Liz Kong, Meng Xu, Licong Yang, Shanshan Liu, G. Zheng","doi":"10.1142/S0192415X22500550","DOIUrl":"https://doi.org/10.1142/S0192415X22500550","url":null,"abstract":"The aim of this study is to investigate the molecular mechanism of Smilax china L. polyphenols (SCLPs) in enhancing lipid metabolism and stimulating browning to reduce lipid accumulation in 3T3-L1 adipocytes. SCLP treatment obviously decreased lipid content in a dose-dependent manner (10-40 [Formula: see text]g/mL) in adipocytes. SCLP treatment cooperated with noradrenalin to increase lipolysis. SCLPs reduced the gene expressions of C/EBP[Formula: see text] and Ap2and enhanced the expressions of ACO, CPT, pHSL/HSL, ATGL, and PKA in adipocytes. Furthermore, SCLPs increased mRNA and protein expressions of brown adipocyte-specific factors (UCP-1, PRDM16, PGC-1[Formula: see text], and PPAR[Formula: see text] and mRNA expressions of beige adipocyte-specific markers (CD137, Tbx1, and Tmem26) in 3T3-L1 adipocytes, as well as mitochondrial biogenesis genes (Nrf1 and Tfam). In addition, according to the immunofluorescence staining, the mitochondria number was increased by SCLP. Moreover, [Formula: see text]3-AR or AMPK agonist synergistic SCLPs enhanced the expressions of UCP-1, PRDM16, and PGC-1[Formula: see text]. While [Formula: see text]3-AR or AMPK antagonist significantly decreased the expressions of these brown adipocyte-specific factors, SCLP treatment inhibited the effect of antagonist to improve the expression of UCP-1, PRDM16, and PGC-1[Formula: see text]. These results indicated that SCLPs may regulate lipid metabolism and stimulate browning via the [Formula: see text]3-AR/AMPK[Formula: see text] signaling pathway. Thus, SCLPs likely have potential therapeutic effects on obesity.","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46630757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}