Pub Date : 2024-08-12DOI: 10.1016/j.fitote.2024.106186
Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by excessive intracellular fat deposition in the hepatocytes, and the development is exacerbated by gut microbiota and bile acids metabolism disorders. Ilex hainanensis Merr. is a traditional medicine of the Zhuang nationality, historically esteemed for its efficacy in lowering blood pressure and lipid levels. This study aimed to investigate the pharmacodynamic effects in NAFLD mice and impacts on gut microbiota and bile acids (BAs) metabolism of I. hainanensis extract (IHA). 16 compounds were identified from IHA by HPLC-DAD-MS analysis. IHA significantly reduced body weight indexs, alanine transaminase (ALT) and aspartate transaminase (AST) activities, improved dyslipidemia and insulin resistance (IR), and effectively ameliorated hepatic steatosis in HFD-induced NAFLD mice. IHA also altered gut microbiota composition, particularly enhancing the abundance of bacteria involved in BAs metabolism, as well as augmented BAs synthesis in the liver and increased fecal excretion. In conclusion, our findings suggest that IHA holds promise in improving NAFLD conditions and modulating gut microbiota and BAs metabolism. These insights contribute to a deeper understanding of the mechanisms underlying IHA-mediated alleviation of lipid accumulation in NAFLD.
非酒精性脂肪肝(NAFLD)是一种以肝细胞内脂肪过度沉积为特征的临床病理综合征,肠道微生物群和胆汁酸代谢紊乱会加剧该病的发展。Ilex hainanensis Merr.是壮族的传统药材,历来被推崇为降血压、降血脂的良药。本研究旨在探讨海南藤提取物(IHA)对非酒精性脂肪肝小鼠的药效学作用以及对肠道微生物群和胆汁酸代谢的影响。通过 HPLC-DAD-MS 分析,从 IHA 中鉴定出 16 种化合物。IHA能明显降低高氟酸膳食诱导的非酒精性脂肪肝小鼠的体重指数、丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)活性,改善血脂异常和胰岛素抵抗(IR),并有效改善肝脏脂肪变性。IHA 还改变了肠道微生物群的组成,特别是提高了参与 BAs 代谢的细菌的丰度,并促进了肝脏中 BAs 的合成和粪便排泄量的增加。总之,我们的研究结果表明,IHA 有望改善非酒精性脂肪肝的状况,调节肠道微生物群和 BAs 代谢。这些见解有助于加深对 IHA 介导的非酒精性脂肪肝脂质积累缓解机制的理解。
{"title":"Effect of Ilex hainanensis Merr. On HFD-induced nonalcoholic fatty liver disease and rebalance of gut microbiota and bile acids metabolism in mice","authors":"","doi":"10.1016/j.fitote.2024.106186","DOIUrl":"10.1016/j.fitote.2024.106186","url":null,"abstract":"<div><p>Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by excessive intracellular fat deposition in the hepatocytes, and the development is exacerbated by gut microbiota and bile acids metabolism disorders. <em>Ilex hainanensis</em> Merr. is a traditional medicine of the Zhuang nationality, historically esteemed for its efficacy in lowering blood pressure and lipid levels. This study aimed to investigate the pharmacodynamic effects in NAFLD mice and impacts on gut microbiota and bile acids (BAs) metabolism of <em>I. hainanensis</em> extract (IHA). 16 compounds were identified from IHA by HPLC-DAD-MS analysis. IHA significantly reduced body weight indexs, alanine transaminase (ALT) and aspartate transaminase (AST) activities, improved dyslipidemia and insulin resistance (IR), and effectively ameliorated hepatic steatosis in HFD-induced NAFLD mice. IHA also altered gut microbiota composition, particularly enhancing the abundance of bacteria involved in BAs metabolism, as well as augmented BAs synthesis in the liver and increased fecal excretion. In conclusion, our findings suggest that IHA holds promise in improving NAFLD conditions and modulating gut microbiota and BAs metabolism. These insights contribute to a deeper understanding of the mechanisms underlying IHA-mediated alleviation of lipid accumulation in NAFLD.</p></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-12DOI: 10.1016/j.fitote.2024.106183
Two new heptapeptides, [1–7-NαC]-crocaorbs A1 (1) and A2 (2), were isolated from the latex of Croton campanulatus. Their structures were determined using NMR spectroscopic techniques, ESI-HRMS data, Marfey's method, and further refined using molecular dynamics with simulated annealing (MD/SA). Molecular dynamics calculations of peptides 1 and 2 demonstrated greater stability in simulations using a biological solvent compared to those using DMSO. Compound 1, the most abundant peptide in latex, was assessed for NO production, antiplasmodial and cytotoxicity activities. The peptide significantly increased nitric oxide (NO) production at concentrations of 40, 20 or 10 μM (17.932 ± 1.1, 18.270 ± 0.9, 18.499 ± 0.7, respectively). Its antiplasmodial activity exhibited limited efficacy, with only 5% inhibition of Plasmodium falciparum 3D7 growth at a concentration of 50 μM. Also, it exhibited no cytotoxic effects in the J774A.1 murine macrophages cell line. This study represents the first report of a phytochemical investigation of the species C. campanulatus, which showed orbitides with distinctive sequences in contrast to other peptides described for the genus Croton and contributes to the study of structural diversity within this particular class of compounds.
{"title":"[1–7-NαC]-Crocaorb A1 and A2, orbitides from the latex of Croton campanulatus","authors":"","doi":"10.1016/j.fitote.2024.106183","DOIUrl":"10.1016/j.fitote.2024.106183","url":null,"abstract":"<div><p>Two new heptapeptides, [1–7-NαC]-crocaorbs A1 (<strong>1</strong>) and A2 (<strong>2</strong>), were isolated from the latex of <em>Croton campanulatus</em>. Their structures were determined using NMR spectroscopic techniques, ESI-HRMS data, Marfey's method, and further refined using molecular dynamics with simulated annealing (MD/SA). Molecular dynamics calculations of peptides <strong>1</strong> and <strong>2</strong> demonstrated greater stability in simulations using a biological solvent compared to those using DMSO. Compound <strong>1</strong>, the most abundant peptide in latex, was assessed for NO production, antiplasmodial and cytotoxicity activities. The peptide significantly increased nitric oxide (NO) production at concentrations of 40, 20 or 10 μM (17.932 ± 1.1, 18.270 ± 0.9, 18.499 ± 0.7, respectively). Its antiplasmodial activity exhibited limited efficacy, with only 5% inhibition of <em>Plasmodium falciparum</em> 3D7 growth at a concentration of 50 μM. Also, it exhibited no cytotoxic effects in the J774A.1 murine macrophages cell line. This study represents the first report of a phytochemical investigation of the species <em>C. campanulatus</em>, which showed orbitides with distinctive sequences in contrast to other peptides described for the genus <em>Croton</em> and contributes to the study of structural diversity within this particular class of compounds.</p></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-10DOI: 10.1016/j.fitote.2024.106179
The dried rhizomes of Paris yunnanensis Franch. have been extensively utilized in traditional Chinese medicine as hemostatic, antitumor, and antimicrobial agents. An examination of classical texts and renowned Chinese medical formulations showcased its efficacy in acne treatment. Presently, there is a significant scarcity of Paris resources. Consider directing attention towards the non-medicinal parts of Paris to mitigate the strain on medicinal resources within this realm. To address these resource limitations, this study investigated the bioactivity and pharmacodynamics of the above-ground parts of Paris (AGPP). A synergistic approach integrating network pharmacology, molecular docking (in silico validation), and animal experimentation (in vivo validation) was employed to elucidate the potential mechanisms underlying the efficacy of AGPP against acne vulgaris in this study. The active constituents in AGPP extracts were identified via UHPLC-Q-Orbitrap HRMS analysis, with their targets extracted for network pharmacological analysis. KEGG pathway analysis unveiled potential therapeutic mechanisms, validated through molecular docking and rat auricular acne model experiments. Comprehensive chemical characterization revealed fifty constituents, including steroidal saponins, flavonoids, amino acids, organic acids, phytohormones, phenolic acids, and alkaloids. Diosgenin, Quercetin, Kaempferol, Ecdysone, and α-linolenic acid were identified as main constituents with acne-treating potential. Core targets included SRC, MAPK3, and MAPK1, with key signaling pathways implicated. Histologically, AGPP mitigated acne-induced follicular dilatation and inflammation, inhibiting inflammatory cytokine production (IL-6, IL-1β, TNF-α). This study offers insight into AGPP's mechanism for acne treatment, laying groundwork for Paris development and drug discovery.
{"title":"Unveiling the hidden potential: Above-ground parts of Paris yunnanensis Franch. Is promise as an anti-acne therapeutic beyond traditional medicinal sites","authors":"","doi":"10.1016/j.fitote.2024.106179","DOIUrl":"10.1016/j.fitote.2024.106179","url":null,"abstract":"<div><p>The dried rhizomes of <em>Paris yunnanensis</em> Franch<em>.</em> have been extensively utilized in traditional Chinese medicine as hemostatic, antitumor, and antimicrobial agents. An examination of classical texts and renowned Chinese medical formulations showcased its efficacy in acne treatment. Presently, there is a significant scarcity of <em>Paris</em> resources. Consider directing attention towards the non-medicinal parts of <em>Paris</em> to mitigate the strain on medicinal resources within this realm. To address these resource limitations, this study investigated the bioactivity and pharmacodynamics of the above-ground parts of <em>Paris</em> (AGPP). A synergistic approach integrating network pharmacology, molecular docking (in silico validation), and animal experimentation (in vivo validation) was employed to elucidate the potential mechanisms underlying the efficacy of AGPP against acne vulgaris in this study. The active constituents in AGPP extracts were identified via UHPLC-Q-Orbitrap HRMS analysis, with their targets extracted for network pharmacological analysis. KEGG pathway analysis unveiled potential therapeutic mechanisms, validated through molecular docking and rat auricular acne model experiments. Comprehensive chemical characterization revealed fifty constituents, including steroidal saponins, flavonoids, amino acids, organic acids, phytohormones, phenolic acids, and alkaloids. Diosgenin, Quercetin, Kaempferol, Ecdysone, and α-linolenic acid were identified as main constituents with acne-treating potential. Core targets included SRC, MAPK3, and MAPK1, with key signaling pathways implicated. Histologically, AGPP mitigated acne-induced follicular dilatation and inflammation, inhibiting inflammatory cytokine production (IL-6, IL-1β, TNF-α). This study offers insight into AGPP's mechanism for acne treatment, laying groundwork for Paris development and drug discovery.</p></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-08DOI: 10.1016/j.fitote.2024.106177
This study was conducted to determine and compare the phenolic compounds, glucosinolate contents and antidiabetic effects of the extracts obtained by ultrasonic and conventional extraction method of the leaves and flowers of the Crambe tataria. The highest antioxidant activity (12.95 mg/mL IC50 value) and total phenolic content (1313.57 mg GAE/100 g fw) were detected in the ultrasonic flower extract. In total flavonoid results, extracts obtained from the flower part of C. tataria had higher values than that of extracts obtained from the leaf part. The most abundant phenolic component in the flower extract was catechin. The highest catechin content in all samples was detected in the ultrasonic flower extract with a value of 374.37 mg/kg. Rutin was the dominant phenolic component in the leaf extract. Rutin values were 654.38 mg/kg and 757.30 mg/kg for conventional and ultrasonic extraction, respectively. In glucosinolate analysis, the highest glucoraphanin content was obtained in flower samples and by conventional extraction method (3466.84 mg/kg). The highest contents of sinigrin (689.97 mg/kg), glucotropaeolin (420.89 mg/kg), glucoerucin (357.27 mg/kg), glucoraphasatin (181.11 mg/kg) and gluconasturtin (66.07 mg/kg) were detected in ultrasonic flower extracts. The highest α-amylase and α-glucosidase enzyme inhibition effects belonged to the ultrasonic flower extract with values of 3.70 mg/mL and 4.89 mg/mL, respectively. As a result, this study determined for the first time that ultrasonic extraction of C. tataria flowers has much higher bioactive components and antidiabetic effects, revealing the potential use of this plant in the fields of medicine, pharmacology and chemistry.
本研究旨在测定和比较用超声波提取法和传统提取法萃取的蝙蝠葛叶和花的酚类化合物、葡萄糖苷酸含量和抗糖尿病作用。超声波花提取物的抗氧化活性(12.95 mg/mL IC50 值)和总酚含量(1313.57 mg GAE/100 g fw)最高。在总黄酮的结果中,从 C. tataria 花部提取物的值高于从叶部提取物的值。花提取物中含量最高的酚类成分是儿茶素。所有样品中儿茶素含量最高的是超声波花提取物,含量为 374.37 毫克/千克。芦丁是叶提取物中最主要的酚类成分。传统提取和超声波提取的芦丁值分别为 654.38 毫克/千克和 757.30 毫克/千克。在葡萄糖苷酸分析中,花朵样品和传统提取法得到的葡萄糖苷酸含量最高(3466.84 毫克/千克)。在超声波花提取物中检测到的西尼格林(689.97 毫克/千克)、葡萄糖苷(420.89 毫克/千克)、葡萄糖醛酸(357.27 毫克/千克)、葡萄糖苷(181.11 毫克/千克)和葡萄糖酸(66.07 毫克/千克)含量最高。超声花提取物对α-淀粉酶和α-葡萄糖苷酶的抑制效果最高,分别为 3.70 毫克/毫升和 4.89 毫克/毫升。因此,本研究首次确定了超声波萃取 C. tataria 花具有更高的生物活性成分和抗糖尿病作用,揭示了该植物在医学、药理学和化学领域的潜在用途。
{"title":"Effect of ultrasonic and conventional extraction on bioactive components, glucosinolate content and antidiabetic activity of Crambe tataria","authors":"","doi":"10.1016/j.fitote.2024.106177","DOIUrl":"10.1016/j.fitote.2024.106177","url":null,"abstract":"<div><p>This study was conducted to determine and compare the phenolic compounds, glucosinolate contents and antidiabetic effects of the extracts obtained by ultrasonic and conventional extraction method of the leaves and flowers of the <em>Crambe tataria</em>. The highest antioxidant activity (12.95 mg/mL IC<sub>50</sub> value) and total phenolic content (1313.57 mg GAE/100 g fw) were detected in the ultrasonic flower extract. In total flavonoid results, extracts obtained from the flower part of <em>C. tataria</em> had higher values than that of extracts obtained from the leaf part. The most abundant phenolic component in the flower extract was catechin. The highest catechin content in all samples was detected in the ultrasonic flower extract with a value of 374.37 mg/kg. Rutin was the dominant phenolic component in the leaf extract. Rutin values were 654.38 mg/kg and 757.30 mg/kg for conventional and ultrasonic extraction, respectively. In glucosinolate analysis, the highest glucoraphanin content was obtained in flower samples and by conventional extraction method (3466.84 mg/kg). The highest contents of sinigrin (689.97 mg/kg), glucotropaeolin (420.89 mg/kg), glucoerucin (357.27 mg/kg), glucoraphasatin (181.11 mg/kg) and gluconasturtin (66.07 mg/kg) were detected in ultrasonic flower extracts. The highest α-amylase and α-glucosidase enzyme inhibition effects belonged to the ultrasonic flower extract with values of 3.70 mg/mL and 4.89 mg/mL, respectively. As a result, this study determined for the first time that ultrasonic extraction of <em>C. tataria</em> flowers has much higher bioactive components and antidiabetic effects, revealing the potential use of this plant in the fields of medicine, pharmacology and chemistry.</p></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-08DOI: 10.1016/j.fitote.2024.106159
Five previously undescribed protopanaxatriol-type saponins, notoginsenosides Ta-Te (1–5), together with eighteen known triterpenoid saponins (6–23) were isolated from the roots of Panax notoginseng. The structures of new compounds were determined by HRESIMS and NMR spectroscopic analyses and chemical methods. Compounds 1 and 2 were the first examples of ginsenosides featuring a 6-deoxy-β-d-glucose moiety from Panax species. Compounds 1–4, 7, 10, 12, 21–22 showed protective effects on L02 cells against the injury of acetaminophen (APAP). Among them, notoginsenoside R1 (12), ginsenoside Rg1 (21), and ginsenoside Re (22) were the most potent ones, with cell viabilities >80%. Moreover, compounds 12 and 22 remarkably alleviated APAP-induced liver injury in mice. These saponins are potential hepatoprotective agents.
{"title":"Triterpenoid saponins from the roots of Panax notoginseng with protective effects against APAP-induced liver injury","authors":"","doi":"10.1016/j.fitote.2024.106159","DOIUrl":"10.1016/j.fitote.2024.106159","url":null,"abstract":"<div><p>Five previously undescribed protopanaxatriol-type saponins, notoginsenosides Ta-Te (<strong>1</strong>–<strong>5</strong>), together with eighteen known triterpenoid saponins (<strong>6</strong>–<strong>23</strong>) were isolated from the roots of <em>Panax notoginseng</em>. The structures of new compounds were determined by HRESIMS and NMR spectroscopic analyses and chemical methods. Compounds <strong>1</strong> and <strong>2</strong> were the first examples of ginsenosides featuring a 6-deoxy-<em>β</em>-<span>d</span>-glucose moiety from <em>Panax</em> species. Compounds <strong>1</strong>–<strong>4</strong>, <strong>7</strong>, <strong>10</strong>, <strong>12</strong>, <strong>21</strong>–<strong>22</strong> showed protective effects on L02 cells against the injury of acetaminophen (APAP). Among them, notoginsenoside R1 (<strong>12</strong>), ginsenoside Rg1 (<strong>21</strong>), and ginsenoside Re (<strong>22</strong>) were the most potent ones, with cell viabilities >80%. Moreover, compounds <strong>12</strong> and <strong>22</strong> remarkably alleviated APAP-induced liver injury in mice. These saponins are potential hepatoprotective agents.</p></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-08DOI: 10.1016/j.fitote.2024.106174
Under the guidance of MS/MS-based molecular networking, five new clerodane diterpenoid glucosides, tinosinesides R-V (1–5), along with 15 known diterpenoids (6–20), were isolated from the stems of Tinospora sinensis. Compound 1 represents the first example of diterpenoid bearing a thio sugar and compound 5 is the first 18,19-dinor-clerodane with cis-fused A/B ring. The structures of the new compounds were elucidated by spectroscopic means, and their absolute configurations were established on the basis of time-dependent density functional theory (TD-DFT) based electronic circular dichroism (ECD) calculation and chemical methods. Selected compounds were evaluated for their immunomodulatory effect and several compounds could enhance the proliferation of B lymphocytes. Preliminary mechanistic studies disclosed that 3 could promote B cell generation and inhibit B cell differentiation.
在基于 MS/MS 的分子网络的指导下,从中华天南星茎中分离出了五种新的萜类二萜糖苷--天南星苷 R-V(1-5),以及 15 种已知的二萜类化合物(6-20)。化合物 1 代表了第一个带有硫糖的二萜类化合物,化合物 5 则是第一个带有顺式融合 A/B 环的 18,19 二甲基-氯丹。这些新化合物的结构是通过光谱手段阐明的,其绝对构型是根据基于时间相关密度泛函理论(TD-DFT)的电子圆二色性(ECD)计算和化学方法确定的。对所选化合物的免疫调节作用进行了评估,其中一些化合物可以促进 B 淋巴细胞的增殖。初步机理研究发现,3 能促进 B 细胞生成并抑制 B 细胞分化。
{"title":"Targeted discovery of clerodane diterpenoids from Tinospora sinensis as immunomodulatory agents","authors":"","doi":"10.1016/j.fitote.2024.106174","DOIUrl":"10.1016/j.fitote.2024.106174","url":null,"abstract":"<div><p>Under the guidance of MS/MS-based molecular networking, five new clerodane diterpenoid glucosides, tinosinesides R-V (<strong>1</strong>–<strong>5</strong>), along with 15 known diterpenoids (<strong>6–20</strong>), were isolated from the stems of <em>Tinospora sinensis</em>. Compound <strong>1</strong> represents the first example of diterpenoid bearing a thio sugar and compound <strong>5</strong> is the first 18,19-dinor-clerodane with <em>cis</em>-fused A/B ring. The structures of the new compounds were elucidated by spectroscopic means, and their absolute configurations were established on the basis of time-dependent density functional theory (TD-DFT) based electronic circular dichroism (ECD) calculation and chemical methods. Selected compounds were evaluated for their immunomodulatory effect and several compounds could enhance the proliferation of B lymphocytes. Preliminary mechanistic studies disclosed that <strong>3</strong> could promote B cell generation and inhibit B cell differentiation.</p></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-08DOI: 10.1016/j.fitote.2024.106176
Metabolites produced by the genus Streptomyces are the most important resource for discovering bioactive compounds. In this study, chemical investigation on the metabolites produced by the marine-derived Streptomyces sp. ZZ735 in rice solid medium led to the isolation of eighteen compounds (1–18). Chemical structures of the isolated compounds were determined based on their HRESIMS data and the extensive NMR spectral analyses. Streptonaphthothiazines A (1), B (2), 2-(2-hydroxy-2-methylpropanoylamino)-benzoic acid (7), and streptomycinoic acids A (17), B (18) are characterized as five previously undescribed compounds. The structural backbones of streptonaphthothiazines A (1), B (2) and streptomycinoic acids A (17), B (18) are found from a natural resource for the first time. It is also the first report of 2-(2-methylpropanoylamino)-benzoic acid (3), 2-(2-methylpropanoylamino)-benzamide (4), methyl 2-(3-hydroxypropanoylamino)-benzoate (5), 2-propionylaminobenzamide (6), and (2E)-3-(3-hydroxy-4,5-dimethoxyphenyl)-2-propenoic acid (15) as natural products. Streptonaphthothiazines A (1), B (2) and streptomycinoic acids A (17), B (18) have antiproliferative activity against human glioma U87MG or U251 cells with IC50 values ranging from 31.8 to 37.9 μM.
链霉菌属产生的代谢物是发现生物活性化合物的最重要资源。本研究对海洋链霉菌 ZZ735 在水稻固体培养基中产生的代谢物进行了化学研究,分离出 18 种化合物(1-18)。根据 HRESIMS 数据和大量核磁共振光谱分析,确定了分离化合物的化学结构。链萘噻嗪 A (1)、B (2)、2-(2-羟基-2-甲基丙酰氨基)-苯甲酸 (7) 和链霉素 A (17)、B (18) 是以前未曾描述过的五个化合物。首次从天然资源中发现了链萘噻嗪 A (1)、B (2)和链霉素酸 A (17)、B (18)的结构骨架。这也是首次报道 2-(2-甲基丙酰氨基)-苯甲酸 (3)、2-(2-甲基丙酰氨基)-苯甲酰胺 (4)、2-(3-羟基丙酰氨基)-苯甲酸甲酯 (5)、2-丙酰氨基苯甲酰胺 (6) 和 (2E)-3-(3- 羟基-4,5-二甲氧基苯基)-2-丙烯酸 (15) 的天然产物。链萘噻嗪 A (1)、B (2) 和链霉素 A (17)、B (18) 对人类胶质瘤 U87MG 或 U251 细胞具有抗增殖活性,其 IC50 值介于 31.8 至 37.9 μM 之间。
{"title":"Antiproliferative metabolites against glioma cells from the marine-associated actinomycete Streptomyces sp. ZZ735","authors":"","doi":"10.1016/j.fitote.2024.106176","DOIUrl":"10.1016/j.fitote.2024.106176","url":null,"abstract":"<div><p>Metabolites produced by the genus <em>Streptomyces</em> are the most important resource for discovering bioactive compounds. In this study, chemical investigation on the metabolites produced by the marine-derived <em>Streptomyces</em> sp. ZZ735 in rice solid medium led to the isolation of eighteen compounds (<strong>1</strong>–<strong>18</strong>). Chemical structures of the isolated compounds were determined based on their HRESIMS data and the extensive NMR spectral analyses. Streptonaphthothiazines A (<strong>1</strong>), B (<strong>2</strong>), 2-(2-hydroxy-2-methylpropanoylamino)-benzoic acid (<strong>7</strong>), and streptomycinoic acids A (<strong>17</strong>), B (<strong>18</strong>) are characterized as five previously undescribed compounds. The structural backbones of streptonaphthothiazines A (<strong>1</strong>), B (<strong>2</strong>) and streptomycinoic acids A (<strong>17</strong>), B (<strong>18</strong>) are found from a natural resource for the first time. It is also the first report of 2-(2-methylpropanoylamino)-benzoic acid (<strong>3</strong>), 2-(2-methylpropanoylamino)-benzamide (<strong>4</strong>), methyl 2-(3-hydroxypropanoylamino)-benzoate (<strong>5</strong>), 2-propionylaminobenzamide (<strong>6</strong>), and (2<em>E</em>)-3-(3-hydroxy-4,5-dimethoxyphenyl)-2-propenoic acid (<strong>15</strong>) as natural products. Streptonaphthothiazines A (<strong>1</strong>), B (<strong>2</strong>) and streptomycinoic acids A (<strong>17</strong>), B (<strong>18</strong>) have antiproliferative activity against human glioma U87MG or U251 cells with IC<sub>50</sub> values ranging from 31.8 to 37.9 μM.</p></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-07DOI: 10.1016/j.fitote.2024.106170
Liver fibrosis is a wound-healing process. It can be induced by various chronic liver diseases. Liver fibrosis is characterized by the activation of hepatic stellate cells (HSCs), a key event. However, no effective treatment strategies to cure or alleviate liver fibrosis-induced pathologic changes have yet been developed. Traditional Chinese medicine (TCM) exhibits a good anti-fibrosis action, with few side effects. Gentiana decoction, a TCM also called Longdan Xiegan Tang (LXT), is used for purging the liver in clinical settings. However, the role of LXT in preventing liver fibrosis and the underlying regulatory mechanism have not yet been investigated. This study demonstrates that LXT treatment can protect the liver from the injuries resulting from CCl4-induced liver fibrosis in mice and suppress the activation of HSCs. The mice in the LXT group exhibit litter collagen I and HSC activation marker α-smooth muscle actin (α-SMA) expression. Transcriptome sequencing of the mouse liver tissue reveals that the level of Parkin, a mitophagy marker, decreased in CCl4-induced liver fibrosis. Further study shows that the injection of Parkin-overexpression adeno-associated virus (Parkin–AAV) via the tail vein can reduce CCl4-induced liver fibrogenesis in mice. We conducted a mechanistic study also, which suggests that LXT treatment suppresses the activation of HSCs by upregulating the expression of Parkin. Hence, it can be suggested that LXT inhibits liver fibrosis by activating the Parkin signaling pathway.
{"title":"Gentiana decoction inhibits liver fibrosis and the activation of hepatic stellate cells via upregulating the expression of Parkin","authors":"","doi":"10.1016/j.fitote.2024.106170","DOIUrl":"10.1016/j.fitote.2024.106170","url":null,"abstract":"<div><p>Liver fibrosis is a wound-healing process. It can be induced by various chronic liver diseases. Liver fibrosis is characterized by the activation of hepatic stellate cells (HSCs), a key event. However, no effective treatment strategies to cure or alleviate liver fibrosis-induced pathologic changes have yet been developed. Traditional Chinese medicine (TCM) exhibits a good anti-fibrosis action, with few side effects. Gentiana decoction, a TCM also called Longdan Xiegan Tang (LXT), is used for purging the liver in clinical settings. However, the role of LXT in preventing liver fibrosis and the underlying regulatory mechanism have not yet been investigated. This study demonstrates that LXT treatment can protect the liver from the injuries resulting from CCl<sub>4</sub>-induced liver fibrosis in mice and suppress the activation of HSCs. The mice in the LXT group exhibit litter collagen I and HSC activation marker α-smooth muscle actin (α-SMA) expression. Transcriptome sequencing of the mouse liver tissue reveals that the level of Parkin, a mitophagy marker, decreased in CCl<sub>4</sub>-induced liver fibrosis. Further study shows that the injection of Parkin-overexpression adeno-associated virus (Parkin–AAV) via the tail vein can reduce CCl<sub>4</sub>-induced liver fibrogenesis in mice. We conducted a mechanistic study also, which suggests that LXT treatment suppresses the activation of HSCs by upregulating the expression of Parkin. Hence, it can be suggested that LXT inhibits liver fibrosis by activating the Parkin signaling pathway.</p></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-06DOI: 10.1016/j.fitote.2024.106173
Neuroinflammation and neuronal apoptosis are central pathogenic consequences associated with Alzheimer's Disease (AD) and Parkinson's Disease (PD). Limonin (LM), a tetracyclic triterpenoid available in citrus fruits, has anti-tumor, antioxidant, anti-inflammatory, hepatoprotective, and neuroprotective actions. LM derivative, V-A-4 emerged as a potential neuroprotective drug due to their ability to target multiple molecular pathways intertwined with neuroinflammation and neuronal apoptosis. To date, the treatment of AD and PD is not successful even though the understanding of the mechanism of neuroinflammation and neuronal apoptosis is vast in the literature. Thus, there is an urgent need to identify novel neuroprotective drugs that could target the multiple molecular pathways associated with neuroinflammation and neuronal apoptosis. The various online databases (Google scholar, Pubmed, Scopus) were searched via keywords: limonin, limonin derivatives and neuroprotection. This review highlights the multifunctional nature of LM and derivatives in combating neuroinflammation and neuronal apoptosis by stimulating PI3K/AKT and downregulating TLR4/NF-κB critical pathways. By intervening in the secretion of NO and TNF-α from glial cells, V-A-4 attenuates the damaging cascade of neuroinflammation by suppressing IKK-α and IKK-β. Furthermore, V-A-4 demonstrates its versatility by suppressing the manifestation of miR-146a and miR-155, both intimately linked to neuroinflammation, this review summarized the activities of LM and its derivatives against AD and PD, with a special focus on V-A-4 as an effective neuroprotective drug. V-A-4's ability to stimulate PI3K/AKT signaling further underscores its neuroprotective effect in combating AD and PD. More in-vitro cell line studies are needed to develop V-A-4 as an upcoming neuroprotective compound.
{"title":"Limonin (LM) and its derivatives: Unveiling the neuroprotective and anti-inflammatory potential of LM and V-A-4 in the management of Alzheimer's disease and Parkinson's disease","authors":"","doi":"10.1016/j.fitote.2024.106173","DOIUrl":"10.1016/j.fitote.2024.106173","url":null,"abstract":"<div><p>Neuroinflammation and neuronal apoptosis are central pathogenic consequences associated with Alzheimer's Disease (AD) and Parkinson's Disease (PD). Limonin (LM), a tetracyclic triterpenoid available in citrus fruits, has anti-tumor, antioxidant, anti-inflammatory, hepatoprotective, and neuroprotective actions. LM derivative, V-A-4 emerged as a potential neuroprotective drug due to their ability to target multiple molecular pathways intertwined with neuroinflammation and neuronal apoptosis. To date, the treatment of AD and PD is not successful even though the understanding of the mechanism of neuroinflammation and neuronal apoptosis is vast in the literature. Thus, there is an urgent need to identify novel neuroprotective drugs that could target the multiple molecular pathways associated with neuroinflammation and neuronal apoptosis. The various online databases (Google scholar, Pubmed, Scopus) were searched via keywords: limonin, limonin derivatives and neuroprotection. This review highlights the multifunctional nature of LM and derivatives in combating neuroinflammation and neuronal apoptosis by stimulating PI3K/AKT and downregulating TLR4/NF-κB critical pathways. By intervening in the secretion of NO and TNF-α from glial cells, V-A-4 attenuates the damaging cascade of neuroinflammation by suppressing IKK-α and IKK-β. Furthermore, V-A-4 demonstrates its versatility by suppressing the manifestation of miR-146a and miR-155, both intimately linked to neuroinflammation, this review summarized the activities of LM and its derivatives against AD and PD, with a special focus on V-A-4 as an effective neuroprotective drug. V-A-4's ability to stimulate PI3K/AKT signaling further underscores its neuroprotective effect in combating AD and PD. More in-vitro cell line studies are needed to develop V-A-4 as an upcoming neuroprotective compound.</p></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-06DOI: 10.1016/j.fitote.2024.106151
In present study, seventeen α-nitrile substituted guaiazulene-based chalcone derivatives including twelve new were designed, synthesized, and assayed for antiviral, cytotoxicity and signal pathway activities. All derivatives showed potential antiviral activity towards influenza virus or herpes simplex virus (HSV), 7 g with the substitution of nitro group showed strong effects towards H1N1 virus at 30 μM with inhibitory rate of 66.0%, 7o with thiophene exhibited potent anti HSV-1 activities with inhibitory rate of 65.8%. Moreover, several compounds exhibited inhibitory effects on tumor cells and hypoxia-inducible factor-1 (HIF1) signaling pathways. These results showed that α-nitrile substituted guaiazulene-based chalcones offered a promising framework for the further development of new highly efficient drugs.
{"title":"Design, synthesis and biological activity of α-nitrile substituted guaiazulene-based chalcone derivatives","authors":"","doi":"10.1016/j.fitote.2024.106151","DOIUrl":"10.1016/j.fitote.2024.106151","url":null,"abstract":"<div><p>In present study, seventeen <em>α</em>-nitrile substituted guaiazulene-based chalcone derivatives including twelve new were designed, synthesized, and assayed for antiviral, cytotoxicity and signal pathway activities. All derivatives showed potential antiviral activity towards influenza virus or herpes simplex virus (HSV), <strong>7 g</strong> with the substitution of nitro group showed strong effects towards H1N1 virus at 30 μM with inhibitory rate of 66.0%, <strong>7o</strong> with thiophene exhibited potent anti HSV-1 activities with inhibitory rate of 65.8%. Moreover, several compounds exhibited inhibitory effects on tumor cells and hypoxia-inducible factor-1 (HIF1) signaling pathways. These results showed that <em>α</em>-nitrile substituted guaiazulene-based chalcones offered a promising framework for the further development of new highly efficient drugs.</p></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}