Ming He, Yuqing Zhang, Yuhan Zhai, Yaping Li, Guorui Yang, Shaoxuan Yu, Haifang Xiao, Yuanda Song
Objectives Trilobatin, a glycosylated dihydrochalcone, has been reported to have anti-diabetic properties. However, the underlying mechanism remains unexplained. Methods In this investigation, the regulation of trilobatin on glucose metabolism of insulin resistance (IR)-HepG2 cells and streptozocin (STZ)-induced mice and its mechanism were evaluated. Key findings Different doses of trilobatin (5, 10 and 20 μM) increased glucose consumption, glycogen content, hexokinase (HK), and pyruvate kinase (PK) activity in IR-HepG2 cells. Among them, the HK and PK activity in IR-HepG2 cells treated with 20 μM trilobatin were 1.84 and 2.05 times than those of the IR-group. The overeating, body and tissue weight, insulin levels, liver damage, and lipid accumulation of STZ-induced mice were improved after feeding with different doses of trilobatin (10, 50, and 100 mg/kg/d) for 4 weeks. Compared with STZ-induced mice, fasting blood glucose decreased by 61.11% and fasting insulin (FINS) increased by 48.6% after feeding trilobatin (100 mg/kg/d). Meanwhile, data from quantitative real-time polymerase chain reaction (qRT-PCR) revealed trilobatin ameliorated glycogen synthesis via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) signaling pathway in IR-HepG2 cells and in STZ-induced mice. Furthermore, in vitro and in vivo experiments showed that trilobatin ameliorated oxidative stress by regulating the mRNA expression of nuclear erythroid-2 related factor 2 (Nrf2)/kelch-like ECH associated protein-1 (Keap-1) pathway as well as heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase-1 (NQO-1). Conclusions Our research reveals a novel pharmacological activity of trilobatin: regulating glucose metabolism through PI3K/Akt/GSK-3β and Nrf2/Keap-1 signaling pathways, improving insulin resistance and reducing oxidative stress. Trilobatin can be used as a reliable drug resource for the treatment of glucose metabolism disorders.
{"title":"Trilobatin regulates glucose metabolism by ameliorating oxidative stress and insulin resistance in vivo and in vitro","authors":"Ming He, Yuqing Zhang, Yuhan Zhai, Yaping Li, Guorui Yang, Shaoxuan Yu, Haifang Xiao, Yuanda Song","doi":"10.1093/jpp/rgae035","DOIUrl":"https://doi.org/10.1093/jpp/rgae035","url":null,"abstract":"Objectives Trilobatin, a glycosylated dihydrochalcone, has been reported to have anti-diabetic properties. However, the underlying mechanism remains unexplained. Methods In this investigation, the regulation of trilobatin on glucose metabolism of insulin resistance (IR)-HepG2 cells and streptozocin (STZ)-induced mice and its mechanism were evaluated. Key findings Different doses of trilobatin (5, 10 and 20 μM) increased glucose consumption, glycogen content, hexokinase (HK), and pyruvate kinase (PK) activity in IR-HepG2 cells. Among them, the HK and PK activity in IR-HepG2 cells treated with 20 μM trilobatin were 1.84 and 2.05 times than those of the IR-group. The overeating, body and tissue weight, insulin levels, liver damage, and lipid accumulation of STZ-induced mice were improved after feeding with different doses of trilobatin (10, 50, and 100 mg/kg/d) for 4 weeks. Compared with STZ-induced mice, fasting blood glucose decreased by 61.11% and fasting insulin (FINS) increased by 48.6% after feeding trilobatin (100 mg/kg/d). Meanwhile, data from quantitative real-time polymerase chain reaction (qRT-PCR) revealed trilobatin ameliorated glycogen synthesis via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) signaling pathway in IR-HepG2 cells and in STZ-induced mice. Furthermore, in vitro and in vivo experiments showed that trilobatin ameliorated oxidative stress by regulating the mRNA expression of nuclear erythroid-2 related factor 2 (Nrf2)/kelch-like ECH associated protein-1 (Keap-1) pathway as well as heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase-1 (NQO-1). Conclusions Our research reveals a novel pharmacological activity of trilobatin: regulating glucose metabolism through PI3K/Akt/GSK-3β and Nrf2/Keap-1 signaling pathways, improving insulin resistance and reducing oxidative stress. Trilobatin can be used as a reliable drug resource for the treatment of glucose metabolism disorders.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140630108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
H Pratima, Anita Shiraguppi, Priyadarshini Joojagar, Kamal Shah, Sudharani S Cheeraladinni, P Shivakumar Singh, Suresh kumar Mendem, Nagendra Singh Chauhan
The Phyllanthus genus is very important plant traded as a raw herbal medicine in India. Commonly known as ‘Bhumyamalaki’ (Phyllanthus species) has been used for the prevention and treatment of jaundice. Phyllanthus is rich in diversity of bioactive compounds such as lignans, alkaloids, terpenoids, flavonoids, and tannins. Among some metabolites such as phyllanthin, hypophyllanthin, 8, 9-epoxy brevifolin, brevifolin, quercetin, gallic acid, elagic acid, and brevifolin carboxylate have been shown to have hepatoprotective and antioxidant activity found in this genus. The basic objective of this review was to overview the hepatoprotective activity based on the other available data from various plants of the Phyllanthus species including Phyllanthus amarus, Phyllanhtus urinaria, Phyllanthus fraternus, Phyllanthus maderaspatenis, Phyllanthus simplex, Phyllanthus emblica, Phyllanthus debillis, Phyllanthus tenellus, Phyllanthus polyphyllus, Phyllanthus reticulates, Phyllanthus indofischerii, Phyllanthus acidus, Phyllanthus niruri, Phyllanthus rheedii, Phyllanthus kozhikodianus, and Phyllanthus longiflorus. These species studied had considerable hepatoprotective potential. The secondary data, each in vitro and in vivo studies confirm the capacity of Phyllanthus species used as a remedy for jaundice or liver disease in addition to having antioxidants. Furthermore, it could be concluded that herbal drugs have the least side effects and are taken into considered safe for human health, they are able to substantially alternative synthetic drugs in the future.
{"title":"Phytochemical profile and hepatoprotective potentiality of Phyllanthus genus: a review","authors":"H Pratima, Anita Shiraguppi, Priyadarshini Joojagar, Kamal Shah, Sudharani S Cheeraladinni, P Shivakumar Singh, Suresh kumar Mendem, Nagendra Singh Chauhan","doi":"10.1093/jpp/rgae040","DOIUrl":"https://doi.org/10.1093/jpp/rgae040","url":null,"abstract":"The Phyllanthus genus is very important plant traded as a raw herbal medicine in India. Commonly known as ‘Bhumyamalaki’ (Phyllanthus species) has been used for the prevention and treatment of jaundice. Phyllanthus is rich in diversity of bioactive compounds such as lignans, alkaloids, terpenoids, flavonoids, and tannins. Among some metabolites such as phyllanthin, hypophyllanthin, 8, 9-epoxy brevifolin, brevifolin, quercetin, gallic acid, elagic acid, and brevifolin carboxylate have been shown to have hepatoprotective and antioxidant activity found in this genus. The basic objective of this review was to overview the hepatoprotective activity based on the other available data from various plants of the Phyllanthus species including Phyllanthus amarus, Phyllanhtus urinaria, Phyllanthus fraternus, Phyllanthus maderaspatenis, Phyllanthus simplex, Phyllanthus emblica, Phyllanthus debillis, Phyllanthus tenellus, Phyllanthus polyphyllus, Phyllanthus reticulates, Phyllanthus indofischerii, Phyllanthus acidus, Phyllanthus niruri, Phyllanthus rheedii, Phyllanthus kozhikodianus, and Phyllanthus longiflorus. These species studied had considerable hepatoprotective potential. The secondary data, each in vitro and in vivo studies confirm the capacity of Phyllanthus species used as a remedy for jaundice or liver disease in addition to having antioxidants. Furthermore, it could be concluded that herbal drugs have the least side effects and are taken into considered safe for human health, they are able to substantially alternative synthetic drugs in the future.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140627081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yun Jin, Yihe Dai, Ou Qiao, Pingping Hu, Jiang Han
Aim To understand the regulatory roles of miR-1972 and GZMH in hepatocellular carcinoma (HCC) and explore their potential as therapeutic biomarkers. Methods In vitro verification of the regulation of malignant cell behavior by differential expression of miR-1972 in HCC cells. The GSE113996 dataset was studied using weighted gene co-expression network analysis (WGCNA) and differential expressed genes respectively to identify the key prognostic gene GZMH and assess the effect of its differential expression on the prognosis of the patient. Finally, the regulation of GZMH expression by miR-1972 was verified, and the effect of their combination on HCC cell behavior was analyzed. Results Inhibition of miR-1972 can reduce cell proliferation, migration, and invasion, while overexpression of miR-1972 has the opposite effect in HCC cells. According to the data, a positive prognosis for HCC was linked with higher GZMH expression. Interestingly, miR-1972 was observed to reverse-regulate the expression of GZMH. Besides, the combined regulation of GZMH and miR-1972 has been discovered to affect the cell growth, invasive capacity, and migratory potential of HCC cells, especially the cell cycle arrest in the G2 phase. Conclusions miR-1972 regulates the malignant behavior of HCC cells, especially cell proliferation, by regulating GZMH expression.
{"title":"miR-1972 inhibits hepatocellular carcinoma proliferation by targeting GZMH-mediated DNA replication in the cell cycle","authors":"Yun Jin, Yihe Dai, Ou Qiao, Pingping Hu, Jiang Han","doi":"10.1093/jpp/rgae037","DOIUrl":"https://doi.org/10.1093/jpp/rgae037","url":null,"abstract":"Aim To understand the regulatory roles of miR-1972 and GZMH in hepatocellular carcinoma (HCC) and explore their potential as therapeutic biomarkers. Methods In vitro verification of the regulation of malignant cell behavior by differential expression of miR-1972 in HCC cells. The GSE113996 dataset was studied using weighted gene co-expression network analysis (WGCNA) and differential expressed genes respectively to identify the key prognostic gene GZMH and assess the effect of its differential expression on the prognosis of the patient. Finally, the regulation of GZMH expression by miR-1972 was verified, and the effect of their combination on HCC cell behavior was analyzed. Results Inhibition of miR-1972 can reduce cell proliferation, migration, and invasion, while overexpression of miR-1972 has the opposite effect in HCC cells. According to the data, a positive prognosis for HCC was linked with higher GZMH expression. Interestingly, miR-1972 was observed to reverse-regulate the expression of GZMH. Besides, the combined regulation of GZMH and miR-1972 has been discovered to affect the cell growth, invasive capacity, and migratory potential of HCC cells, especially the cell cycle arrest in the G2 phase. Conclusions miR-1972 regulates the malignant behavior of HCC cells, especially cell proliferation, by regulating GZMH expression.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140626655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objectives The study aimed to investigate the protective effects of dexmedetomidine (DEX) on renal injury caused by acute stress in rats and explore the protective pathways of DEX on rat kidneys in terms of oxidative stress. Methods An acute restraint stress model was utilized, where rats were restrained for 3 hours after a 15-minute swim. Biochemical tests and histopathological sections were conducted to evaluate renal function, along with the measurement of oxidative stress and related pathway proteins. Key findings The open-field experiments validated the successful establishment of the acute stress model. Acute stress-induced renal injury led to increased NADPH oxidase 4 (NOX4) protein expression and decreased expression levels of nuclear transcription factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H: quinone oxidoreductase 1 (NQO1). Following DEX treatment, there was a significant reduction in renal NOX4 expression. The DEX-treated group exhibited normalized renal biochemical results and less damage observed in pathological sections compared to the acute stress group. Conclusions The findings suggest that DEX treatment during acute stress can impact the NOX4/Nrf2/HO-1/NQO1 signaling pathway and inhibit oxidative stress, thereby preventing acute stress-induced kidney injury. Additionally, DEX shows promise for clinical applications in stress syndromes.
{"title":"Dexmedetomidine affects the NOX4/Nrf2 pathway to improve renal antioxidant capacity","authors":"Haotian Yang, Yongping Chen, Zhiqiang Wang, Yuxiang Huang, Zhigang Ma, Yue Zou, Jiaqiang Dong, Hong Zhang, Mingdong Huo, Mingzhe Lv, Xuesong Liu, Guohua Zhang, Shuang Wang, Kun Yang, Peng Zhong, Botao Jiang, Yuhong Kou, Zhifeng Chen","doi":"10.1093/jpp/rgae044","DOIUrl":"https://doi.org/10.1093/jpp/rgae044","url":null,"abstract":"Objectives The study aimed to investigate the protective effects of dexmedetomidine (DEX) on renal injury caused by acute stress in rats and explore the protective pathways of DEX on rat kidneys in terms of oxidative stress. Methods An acute restraint stress model was utilized, where rats were restrained for 3 hours after a 15-minute swim. Biochemical tests and histopathological sections were conducted to evaluate renal function, along with the measurement of oxidative stress and related pathway proteins. Key findings The open-field experiments validated the successful establishment of the acute stress model. Acute stress-induced renal injury led to increased NADPH oxidase 4 (NOX4) protein expression and decreased expression levels of nuclear transcription factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H: quinone oxidoreductase 1 (NQO1). Following DEX treatment, there was a significant reduction in renal NOX4 expression. The DEX-treated group exhibited normalized renal biochemical results and less damage observed in pathological sections compared to the acute stress group. Conclusions The findings suggest that DEX treatment during acute stress can impact the NOX4/Nrf2/HO-1/NQO1 signaling pathway and inhibit oxidative stress, thereby preventing acute stress-induced kidney injury. Additionally, DEX shows promise for clinical applications in stress syndromes.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140613308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objectives Ranunculus L. genus contains 413 species, and it is the biggest genus in the family Ranunculaceae Juss. This review is to provide botanical characteristics, traditional uses, phytochemistry, pharmacology, toxicity, and pharmaceutical preparations of the genus Ranunculus. Key findings The genus Ranunculus contains flavonoids, organic acids, coumarins, lactones, glycosides, sterols, polysaccharides, and trace elements. These chemical constituents complement the pharmacological actions and work together to exert anti-inflammatory, anticancer, antitubercular, antibacterial, antimalarial, etc. Those traditional Chinese medicine characteristics, like clearing away heat and detoxification, make this genus significant in ethnic medicine. The progress in research and the development of various pharmaceutical preparations made it appear in epidemiological and clinical studies. Summary The genus Ranunculus has attracted the attention of experts and scholars in many fields due to its unique advantages. However, there are many species that are not scientifically investigated. The toxicity issues are also a huge concern. Fortunately, the toxicity can be overcome via special processes like drying or heating and by choosing a safe extraction solvent, such as water thus ensuring the safety of medication. Pharmaceutical preparations containing the plants from Ranunculus have gratifying clinical value, but they are not promoted sufficiently. Therefore, further research should be carried out to promote the genus for its health benefits to humans.
{"title":"The genus Ranunculus L. (Ranunculus) in Asia: a review of its botany, traditional uses, phytochemistry, pharmacology, toxicity, and pharmaceutical preparations","authors":"Yun-Lei Dai, Qing-Zhi Liu, Jian Wang, Meng Sun, Feng-Jv Niu, Hao-Cheng Wei, Chang-Zheng Zhou, Li Zhang","doi":"10.1093/jpp/rgad085","DOIUrl":"https://doi.org/10.1093/jpp/rgad085","url":null,"abstract":"Objectives Ranunculus L. genus contains 413 species, and it is the biggest genus in the family Ranunculaceae Juss. This review is to provide botanical characteristics, traditional uses, phytochemistry, pharmacology, toxicity, and pharmaceutical preparations of the genus Ranunculus. Key findings The genus Ranunculus contains flavonoids, organic acids, coumarins, lactones, glycosides, sterols, polysaccharides, and trace elements. These chemical constituents complement the pharmacological actions and work together to exert anti-inflammatory, anticancer, antitubercular, antibacterial, antimalarial, etc. Those traditional Chinese medicine characteristics, like clearing away heat and detoxification, make this genus significant in ethnic medicine. The progress in research and the development of various pharmaceutical preparations made it appear in epidemiological and clinical studies. Summary The genus Ranunculus has attracted the attention of experts and scholars in many fields due to its unique advantages. However, there are many species that are not scientifically investigated. The toxicity issues are also a huge concern. Fortunately, the toxicity can be overcome via special processes like drying or heating and by choosing a safe extraction solvent, such as water thus ensuring the safety of medication. Pharmaceutical preparations containing the plants from Ranunculus have gratifying clinical value, but they are not promoted sufficiently. Therefore, further research should be carried out to promote the genus for its health benefits to humans.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140613307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objectives Achyranthes bidentata Blume (A. bidentata) is a plant of Amaranthaceae family, and its root is the main medicinal part, named “Huai-Niu-Xi.” It is used to expel blood stasis through menstruation, tonify liver and kidney, strengthen muscles and bones, and induce diuresis. This review aimed to provide a systematic summary of botany, traditional uses, phytochemistry, pharmacology, and toxicology of A. bidentata. Methods The present review covers the literature survey. The data have been collected from various journals, books, and some of the electronic search via Internet-based information such as Web of Science, PubMed, Google Scholar, Google patents, CNKI, SpringerLink, online electronic journals, and ScienceDirect. Key findings So far, more than 270 metabolites have been isolated from A. bidentata, including terpenoids, steroids, alkaloids, flavonoids, and so on. Among them, terpenoids and steroids are the main metabolites. The extract and metabolites exert multiple pharmacological activities such as alleviating osteoarthritis effect, antiosteoporosis activity, neuroprotective effect, antidiabetic activity-associated complications, immunoregulatory activity, and so on. Summary Some traditional uses of A. bidentata need further in-depth studies to confirm. Similarly, the separation and screening of active compounds, as well as the corresponding molecular mechanisms of action of compounds, are also needed to be studied.
目标 牛膝（Achyranthes bidentata Blume，A. bidentata）是苋科植物，其根是主要药用部分，名为 "怀牛膝"。怀牛膝具有通经化瘀、补肝肾、强筋骨、利尿等功效。本综述旨在系统地总结淮牛膝的植物学、传统用途、植物化学、药理学和毒理学。方法 本综述涉及文献调查。数据收集自各种期刊、书籍，以及通过网络信息进行的部分电子检索，如 Web of Science、PubMed、Google Scholar、Google Patents、CNKI、SpringerLink、在线电子期刊和 ScienceDirect。主要发现 目前，已从双尾杉中分离出 270 多种代谢物，包括萜类、甾体、生物碱、黄酮类等。其中，萜类和类固醇是主要的代谢产物。提取物和代谢物具有多种药理活性，如缓解骨关节炎、抗骨质疏松症、神经保护作用、抗糖尿病相关并发症、免疫调节活性等。小结 A. bidentata 的一些传统用途还需要进一步的深入研究来证实。同样，活性化合物的分离和筛选，以及相应化合物的分子作用机制也有待研究。
{"title":"Achyranthes bidentata Blume (Amaranthaceae): a review of its botany, traditional uses, phytochemistry, pharmacology, and toxicology","authors":"Yue-Ru Chen, Ying-shuo Niu, Hong-Lei Zhou","doi":"10.1093/jpp/rgae012","DOIUrl":"https://doi.org/10.1093/jpp/rgae012","url":null,"abstract":"Objectives Achyranthes bidentata Blume (A. bidentata) is a plant of Amaranthaceae family, and its root is the main medicinal part, named “Huai-Niu-Xi.” It is used to expel blood stasis through menstruation, tonify liver and kidney, strengthen muscles and bones, and induce diuresis. This review aimed to provide a systematic summary of botany, traditional uses, phytochemistry, pharmacology, and toxicology of A. bidentata. Methods The present review covers the literature survey. The data have been collected from various journals, books, and some of the electronic search via Internet-based information such as Web of Science, PubMed, Google Scholar, Google patents, CNKI, SpringerLink, online electronic journals, and ScienceDirect. Key findings So far, more than 270 metabolites have been isolated from A. bidentata, including terpenoids, steroids, alkaloids, flavonoids, and so on. Among them, terpenoids and steroids are the main metabolites. The extract and metabolites exert multiple pharmacological activities such as alleviating osteoarthritis effect, antiosteoporosis activity, neuroprotective effect, antidiabetic activity-associated complications, immunoregulatory activity, and so on. Summary Some traditional uses of A. bidentata need further in-depth studies to confirm. Similarly, the separation and screening of active compounds, as well as the corresponding molecular mechanisms of action of compounds, are also needed to be studied.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140596831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wonjun Cho, Mineui Hong, Enas H Mobarak, Oğuzhan Birdal, Min Chan Lim, Min Seok Jung, Soon Auck Hong, Ji Hoon Jeong, Tae Woo Jung
Objectives Madecassoside (MA) is a triterpene derived from Centella asiatica that has been recognized for its antioxidant and anti-inflammatory properties in various disease models. However, its direct impact on cultured white adipocytes and the underlying mechanisms, mainly through gene knockdown, have not been thoroughly explored. Methods Western blot analysis was utilized to assess the expression levels of various proteins, while oil red O staining was used to measure lipid deposition. The adipocyte shapes were confirmed using H&E staining. Key findings MA treatment enhanced browning and lipolysis in 3T3-L1 adipocytes and adipose tissue from experimental mice while suppressing lipogenesis. Furthermore, MA treatment increased the expression of PPARα and FGF21 in 3T3-L1 adipocytes as well as the secretion of FGF21 into the culture medium. Knockdown of PPARα or FGF21 using siRNA diminished the effects of MA on lipid metabolism in cultured adipocytes. Conclusions These findings demonstrate that MA promotes thermogenic browning and lipolysis while inhibiting adipocyte lipogenesis, thus showing the potential for attenuating obesity. The study suggested that MA could be a viable therapeutic approach for treating obesity.
目的 马黛茶苷（MA）是从积雪草中提取的一种三萜类化合物，它在各种疾病模型中的抗氧化和抗炎特性已得到公认。然而，它对培养的白色脂肪细胞的直接影响及其内在机制（主要是通过基因敲除）尚未得到深入探讨。方法 利用 Western 印迹分析评估各种蛋白质的表达水平，同时利用油红 O 染色测量脂质沉积。用 H&E 染色法确认脂肪细胞的形状。主要发现 MA 处理增强了 3T3-L1 脂肪细胞和实验小鼠脂肪组织的褐变和脂肪分解，同时抑制了脂肪生成。此外，MA 处理还能增加 PPARα 和 FGF21 在 3T3-L1 脂肪细胞中的表达以及 FGF21 在培养液中的分泌。使用 siRNA 敲除 PPARα 或 FGF21 可减弱 MA 对培养脂肪细胞脂质代谢的影响。结论 这些研究结果表明，MA 在抑制脂肪细胞脂肪生成的同时，还能促进产热性褐变和脂肪分解，因此具有减轻肥胖的潜力。研究表明，MA 是一种治疗肥胖症的可行方法。
{"title":"Madecassoside modulates lipid metabolism in visceral adipocytes: exploring the browning, lipolysis, and lipogenesis mechanisms for potential obesity treatment","authors":"Wonjun Cho, Mineui Hong, Enas H Mobarak, Oğuzhan Birdal, Min Chan Lim, Min Seok Jung, Soon Auck Hong, Ji Hoon Jeong, Tae Woo Jung","doi":"10.1093/jpp/rgae042","DOIUrl":"https://doi.org/10.1093/jpp/rgae042","url":null,"abstract":"Objectives Madecassoside (MA) is a triterpene derived from Centella asiatica that has been recognized for its antioxidant and anti-inflammatory properties in various disease models. However, its direct impact on cultured white adipocytes and the underlying mechanisms, mainly through gene knockdown, have not been thoroughly explored. Methods Western blot analysis was utilized to assess the expression levels of various proteins, while oil red O staining was used to measure lipid deposition. The adipocyte shapes were confirmed using H&E staining. Key findings MA treatment enhanced browning and lipolysis in 3T3-L1 adipocytes and adipose tissue from experimental mice while suppressing lipogenesis. Furthermore, MA treatment increased the expression of PPARα and FGF21 in 3T3-L1 adipocytes as well as the secretion of FGF21 into the culture medium. Knockdown of PPARα or FGF21 using siRNA diminished the effects of MA on lipid metabolism in cultured adipocytes. Conclusions These findings demonstrate that MA promotes thermogenic browning and lipolysis while inhibiting adipocyte lipogenesis, thus showing the potential for attenuating obesity. The study suggested that MA could be a viable therapeutic approach for treating obesity.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140597219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We purposed to explore the consequences of the use quercetin and fisetin alone and in combination with pregabalin and gabapentin, which are used in the management of neuropathic pain, and on neuropathic pain in general. The anti-allodynic effect of various doses (5, 10, and 20 mg/kg) of quercetin and fisetin, both singly and in combination with pregabalin and gabapentin, was evaluated by developing a neuropathic pain model induced by chronic constrictive nerve damage in rats. The effectiveness of these flavonoids was investigated by combining them with gabapentin (50 mg/kg) and pregabalin (15 mg/kg), choosing the effectual dose of 10 mg/kg and the dose of 5 mg/kg, which did not show significant antiallodynic effects. In groups combined with gabapentin and pregabalin, it was determined that they showed a significant antiallodynic effect compared with 50 mg/kg gabapentin and 15 mg/kg pregabalin. In conclusion, in our combination studies, it was observed that the effectiveness of gabapentin and pregabalin, was increased and the duration of effect was prolonged when used with lower doses of flavonoids. Based on these findings; it is possible to say that quercetin and fisetin are potential agents that can be used alone or in combination with other effective treatments to alleviate neuropathic pain.
{"title":"Use of kersetin and fisetin flavonoids in combination with pregabalin and gabapentin in the treatment of neuropathic pain","authors":"Elif Karabacak, Hazal Eken, Ilhem Dallali, Rana Arslan","doi":"10.1093/jpp/rgae034","DOIUrl":"https://doi.org/10.1093/jpp/rgae034","url":null,"abstract":"We purposed to explore the consequences of the use quercetin and fisetin alone and in combination with pregabalin and gabapentin, which are used in the management of neuropathic pain, and on neuropathic pain in general. The anti-allodynic effect of various doses (5, 10, and 20 mg/kg) of quercetin and fisetin, both singly and in combination with pregabalin and gabapentin, was evaluated by developing a neuropathic pain model induced by chronic constrictive nerve damage in rats. The effectiveness of these flavonoids was investigated by combining them with gabapentin (50 mg/kg) and pregabalin (15 mg/kg), choosing the effectual dose of 10 mg/kg and the dose of 5 mg/kg, which did not show significant antiallodynic effects. In groups combined with gabapentin and pregabalin, it was determined that they showed a significant antiallodynic effect compared with 50 mg/kg gabapentin and 15 mg/kg pregabalin. In conclusion, in our combination studies, it was observed that the effectiveness of gabapentin and pregabalin, was increased and the duration of effect was prolonged when used with lower doses of flavonoids. Based on these findings; it is possible to say that quercetin and fisetin are potential agents that can be used alone or in combination with other effective treatments to alleviate neuropathic pain.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140596714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objectives To get a better understanding of the scientific values of flavone scutellarein (SCT), and to encourage its applications in human health, the current review systematically summarizes the natural observation, biosynthesis, synthesis, pharmacology, pharmacokinetics, and recent synthetic advances Key findings Scientific sources to search for references included Google Scholar, Scopus, Web of Science, PubMed, Sci-Finder, and journal websites. The references have been collected from the 1970s to the present. “Scutellarein” is the most meaningful keyword to search for publications, in which it was used alone or in combination with other keywords. Summarys SCT as a hydrophobic flavonoid can be found in various medicinal plants of the families Lamiaceae, Compositae, and Verbenaceae. Flavone SCT has drawn much interest due to its wide pharmacological effects, such as anticancer, anti-inflammation, antioxidant, antiobesity, and vasorelaxant. The SCT treatments also possessed a lot of positive results in the neuron, liver, heart, lung, kidney, bone, and skin protective experiments, and human sperm function enhancement. Its underlying mechanism of action may relate to the apoptotic program and cytokine inhibition by regulating a panel of the signaling pathway, e.g., NF-κB (nuclear factor kappa B)/MAPK (mitogen-activated protein kinase), IκBa (nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitors alpha)/NF-κB, TRAF2 (tumor necrosis factor receptor-associated factor 2)/NF-κB, and PTEN (phosphatase and tension homologue deleted on chromosome 10)/Akt (protein kinase B)/NF-κB. In addition, the metabolic actions and synthetic derivative promotions of SCT were mostly based on the substitution of hydroxyl groups. Collectively, the studies that aim to highlight the role of scutellarein in preclinical and clinical treatments are urgently needed. More and more experiments to improve its bioavailability are expected.
{"title":"Scutellarein: a review of chemistry and pharmacology","authors":"Nguyen Thi Thoa, Ninh The Son","doi":"10.1093/jpp/rgae039","DOIUrl":"https://doi.org/10.1093/jpp/rgae039","url":null,"abstract":"Objectives To get a better understanding of the scientific values of flavone scutellarein (SCT), and to encourage its applications in human health, the current review systematically summarizes the natural observation, biosynthesis, synthesis, pharmacology, pharmacokinetics, and recent synthetic advances Key findings Scientific sources to search for references included Google Scholar, Scopus, Web of Science, PubMed, Sci-Finder, and journal websites. The references have been collected from the 1970s to the present. “Scutellarein” is the most meaningful keyword to search for publications, in which it was used alone or in combination with other keywords. Summarys SCT as a hydrophobic flavonoid can be found in various medicinal plants of the families Lamiaceae, Compositae, and Verbenaceae. Flavone SCT has drawn much interest due to its wide pharmacological effects, such as anticancer, anti-inflammation, antioxidant, antiobesity, and vasorelaxant. The SCT treatments also possessed a lot of positive results in the neuron, liver, heart, lung, kidney, bone, and skin protective experiments, and human sperm function enhancement. Its underlying mechanism of action may relate to the apoptotic program and cytokine inhibition by regulating a panel of the signaling pathway, e.g., NF-κB (nuclear factor kappa B)/MAPK (mitogen-activated protein kinase), IκBa (nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitors alpha)/NF-κB, TRAF2 (tumor necrosis factor receptor-associated factor 2)/NF-κB, and PTEN (phosphatase and tension homologue deleted on chromosome 10)/Akt (protein kinase B)/NF-κB. In addition, the metabolic actions and synthetic derivative promotions of SCT were mostly based on the substitution of hydroxyl groups. Collectively, the studies that aim to highlight the role of scutellarein in preclinical and clinical treatments are urgently needed. More and more experiments to improve its bioavailability are expected.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140603453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhe Chen, Man Wang, Xiang Lv, Yannan Xu, Xionghui Wang, Bai Li, Changquan Ling, Juan Du
Objectives: Sanshimao (SSM) is a traditional Chinese medicine formula for advanced hepatocellular carcinoma (HCC). This study was designed to investigate the effect of SSM on HCC-induced angiogenesis and to explore the potential mechanism.
Methods: The endothelial cells were cultured with HCC cells conditioned medium in the 1% oxygen atmosphere to imitate tumor hypoxia microenvironment. EA.hy926 cells migration and tubulogenesis were detected by tube formation and scratch-wound assay. The protein microarray was employed to explore SSM-targeted proteins in Huh7 cells. We also established an animal model to observe the effects of SSM on angiogenesis in vivo.
Results: The data indicated that SSM reduced HCC-induced migration and tube formation of EA.hy926 cells at low dose under hypoxic conditions. These effects might be partly owing to suppression of HIF-1α-induced vascular endothelial growth factorα expression in Huh7 cells. Moreover, this inhibition was in an MKK6/P38-dependent way. Besides, Huh7 subcutaneous tumor models in nude mice further demonstrated the inhibition of SSM on tumor weight might be exerted partly by reduction of angiogenesis via blocking MKK6/P38 signaling pathways.
Conclusion: SSM inhibits HCC-induced pro-angiogenesis under hypoxic conditions via suppression of MKK6/P38 signaling pathways, which is favorable for HCC tumor growth.
{"title":"Sanshimao formula inhibits the hypoxia-induced pro-angiogenesis of hepatocellular carcinoma cells partly through regulating MKK6/p38 signaling pathway.","authors":"Zhe Chen, Man Wang, Xiang Lv, Yannan Xu, Xionghui Wang, Bai Li, Changquan Ling, Juan Du","doi":"10.1093/jpp/rgad086","DOIUrl":"10.1093/jpp/rgad086","url":null,"abstract":"<p><strong>Objectives: </strong>Sanshimao (SSM) is a traditional Chinese medicine formula for advanced hepatocellular carcinoma (HCC). This study was designed to investigate the effect of SSM on HCC-induced angiogenesis and to explore the potential mechanism.</p><p><strong>Methods: </strong>The endothelial cells were cultured with HCC cells conditioned medium in the 1% oxygen atmosphere to imitate tumor hypoxia microenvironment. EA.hy926 cells migration and tubulogenesis were detected by tube formation and scratch-wound assay. The protein microarray was employed to explore SSM-targeted proteins in Huh7 cells. We also established an animal model to observe the effects of SSM on angiogenesis in vivo.</p><p><strong>Results: </strong>The data indicated that SSM reduced HCC-induced migration and tube formation of EA.hy926 cells at low dose under hypoxic conditions. These effects might be partly owing to suppression of HIF-1α-induced vascular endothelial growth factorα expression in Huh7 cells. Moreover, this inhibition was in an MKK6/P38-dependent way. Besides, Huh7 subcutaneous tumor models in nude mice further demonstrated the inhibition of SSM on tumor weight might be exerted partly by reduction of angiogenesis via blocking MKK6/P38 signaling pathways.</p><p><strong>Conclusion: </strong>SSM inhibits HCC-induced pro-angiogenesis under hypoxic conditions via suppression of MKK6/P38 signaling pathways, which is favorable for HCC tumor growth.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139642437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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