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Preclinical In Vitro Investigation of MDM2 Inhibition in Combination with Antiangiogenic Therapy for Breast Cancer Treatment MDM2抑制联合抗血管生成治疗乳腺癌的临床前体外研究
IF 2.5 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-02-20 DOI: 10.3390/scipharm91010012
A. Alaseem, Khalid Alhazzani, A. Z. Alanazi, Yasser Alqarni, M. Algahtani, A. Alhamed, Glowi A Alasiri, Fahad T. Alotaibi, Talha Jawaid, J. Aldali
Background: Combining antiangiogenic drugs with other chemotherapeutic drugs has been found to produce superior therapeutic outcomes and prevent drug resistance in a variety of cancers. Methods: Experimental assays such as the MTT assay, flow cytometry, western blotting, and qPCR have been used to evaluate the efficacy of combination therapy. Results: When compared to controls and monotherapies, the combination treatment of axitinib and idasanutlin demonstrated a substantial decrease in cell viability at lower doses, a significant decrease in migration, and a shift toward early and late apoptosis. This study examined major apoptotic, metastatic, and angiogenic factors, including MDM2, p21, BCL-2, BCL-XL, and MMP9, which have showed differential expressions at the protein and mRNA levels after combination. Axitinib and idasanutlin decreased tumorigenesis and migration in vitro in the MCF-7 cell line when compared to other chemotherapeutic medications. The suggested mechanisms of the antitumorigenic effect of the combination therapy may depend on its capacity to promote the production of apoptotic markers and reduce antiapoptotic markers. Conclusions: Treatments with axitinib and idasanutlin demonstrated effective therapeutic targeting of the primary angiogenic growth factor and, consequently, the pro-metastatic arbitrators. This will not only eliminate cancer cells but also stop other malignant processes and ultimately reduce the metastatic cascade.
背景:抗血管生成药物与其他化疗药物相结合已被发现可产生优越的治疗效果,并可预防各种癌症的耐药性。方法:采用MTT比色法、流式细胞术、免疫印迹法和qPCR等实验方法评价联合治疗的疗效。结果:与对照组和单一疗法相比,阿西替尼和伊达那素的联合治疗显示,在较低剂量下,细胞活力显著降低,迁移显著减少,并向早期和晚期凋亡转变。本研究检测了主要的凋亡、转移和血管生成因子,包括MDM2、p21、BCL-2、BCL-XL和MMP9,这些因子在组合后在蛋白质和mRNA水平上表现出差异表达。与其他化疗药物相比,Axitinib和idasanutlin在体外降低了MCF-7细胞系中的肿瘤发生和迁移。联合治疗的抗肿瘤作用的机制可能取决于其促进凋亡标志物产生和减少抗凋亡标志物的能力。结论:阿西替尼和伊达那素治疗显示出对原发性血管生成生长因子的有效治疗靶向性,从而对促转移仲裁者具有治疗作用。这不仅可以消灭癌症细胞,还可以阻止其他恶性过程,最终减少转移级联。
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引用次数: 2
Long-Term Paracetamol Treatment Impairs Cognitive Function and Brain-Derived Neurotrophic Factor in Adult Rat Brain 对乙酰氨基酚长期治疗对成年大鼠大脑认知功能和脑源性神经营养因子的影响
IF 2.5 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-02-13 DOI: 10.3390/scipharm91010011
Laddawan Lalert, Nutnicha Tantarungsee, Tipthanan Chotipinit, Wilawan Ji-au, A. Srikiatkhachorn, S. Maneesri-le Grand
Paracetamol (acetaminophen, APAP) is known as a safe pain reliever; however, its negative effects on the central nervous system have gradually been reported. We examined alterations in learning and memory, and brain-derived neurotrophic factor (BDNF) expression in the frontal cortex and hippocampus at different durations of APAP treatment in rats. Novel object recognition (NOR) and Morris water maze (MWM) paradigms were used to assess learning and memory in rats fed with 200 mg/kg APAP at single-dose, 15-day or 30-day treatments. BDNF expression was evaluated through immunohistochemistry and Western blotting. The single-dose APAP treatment did not alter the NOR performance. However, deficits in the NOR and MWM capacities were detected in the rats with longer durations of APAP treatment. An analysis of BDNF expression revealed no significant change in BDNF expression in the single-dose APAP treatment, while rats given APAP for extended periods as treatment showed a significant decrement in this protein in the frontal cortex and hippocampus. Short-term APAP treatment has no effect on learning and memory, or BDNF expression; however, long-term APAP exposure causes cognitive impairment. The diminishment of the BDNF level in the frontal cortex and hippocampus due to the long period of treatment with APAP may at least in part be involved in altered learning and memory in rats.
对乙酰氨基酚是一种安全的止痛药;然而,它对中枢神经系统的负面影响已逐渐被报道。我们检测了APAP治疗不同持续时间大鼠额叶皮层和海马的学习记忆和脑源性神经营养因子(BDNF)表达的变化。使用新的对象识别(NOR)和Morris水迷宫(MWM)范式来评估单剂量、15天或30天处理下喂食200mg/kg APAP的大鼠的学习和记忆。通过免疫组织化学和蛋白质印迹评估BDNF的表达。单剂量APAP治疗没有改变NOR的表现。然而,在APAP治疗持续时间较长的大鼠中检测到NOR和MWM能力的缺陷。对BDNF表达的分析显示,在单剂量APAP治疗中,BDNF表达没有显著变化,而长期给予APAP治疗的大鼠额叶皮层和海马中的BDNF表达显著减少。短期APAP治疗对学习记忆或BDNF表达没有影响;然而,长期接触APAP会导致认知障碍。由于APAP的长期治疗,额叶皮层和海马中BDNF水平的降低可能至少部分与大鼠学习和记忆的改变有关。
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引用次数: 0
Comparison of Substance Sources in Experimental Antimicrobial Susceptibility Testing 实验药敏试验中物质来源的比较
IF 2.5 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-02-09 DOI: 10.3390/scipharm91010010
Filip Bielec, M. Brauncajs, D. Pastuszak-Lewandoska
Funding is often a constraint when planning research, especially in countries where basic research is underfunded. Researchers must take into account these limitations, e.g., in relation to the selection of appropriate reagents, the source of which may affect the study’s final results. The aim of this article was to compare the results of bacteria susceptibility testing using three different sources of antimicrobial: the pure powder available from the supplier and two tablet formulations with different excipients. The chosen substance was furazidin (nitrofuran derivative). The susceptibility was tested on a group of 45 uropathogenic Enterobacterales using both microdilution and disk diffusion methods. The obtained results indicated that despite the relatively higher price, the powder appeared to be the best substance for scientific purposes, especially for quantitative determinations.
在规划研究时,资金往往是一个制约因素,特别是在基础研究资金不足的国家。研究人员必须考虑到这些限制,例如,在适当试剂的选择方面,其来源可能会影响研究的最终结果。本文的目的是比较使用三种不同来源的抗菌药物的细菌敏感性测试结果:供应商提供的纯粉末和两种不同赋形剂的片剂配方。所选物质为呋喃吡啶(硝基呋喃衍生物)。采用微量稀释法和纸片扩散法对45株尿路致病性肠杆菌进行了药敏试验。所得结果表明,尽管价格相对较高,但该粉末似乎是科学目的的最佳物质,特别是用于定量测定。
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引用次数: 2
Antimicrobial Activity of Novel Deep Eutectic Solvents 新型深共晶溶剂的抗菌活性研究
IF 2.5 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-02-08 DOI: 10.3390/scipharm91010009
N. Akbar, N. Khan, T. Ibrahim, Mustafa I. Khamis, A. Khan, Ahmad M. Alharbi, Hasan Alfahemi, R. Siddiqui
Herein, we utilized several deep eutectic solvents (DES) that were based on hydrogen donors and hydrogen acceptors for their antibacterial application. These DES were tested for their bactericidal activities against Gram-positive (Streptococcus pyogenes, Bacillus cereus, Streptococcus pneumoniae, and methicillin-resistant Staphylococcus aureus) and Gram-negative (Escherichia coli K1, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Serratia marcescens) bacteria. Using lactate dehydrogenase assays, DES were evaluated for their cytopathic effects towards human cells. Results from antibacterial tests revealed that DES prepared from the combination of methyl-trioctylammonium chloride and glycerol (DES-4) and DES prepared form methyl-trioctylammonium chloride and fructose (DES-11) at a 2 µL dose showed broad-spectrum antibacterial behavior and had the highest bactericidal activity. Moreover, DES-4 showed 40% and 68% antibacterial activity against P. aeruginosa and E. coli K1, respectively. Similarly, DES-11 eliminated 65% and 61% E. coli K1 and P. aeruginosa, respectively. Among Gram-positive bacteria, DES-4 showed important antibacterial activity, inhibiting 75% of B. cereus and 51% of S. pneumoniae. Likewise, DES-11 depicted 70% B. cereus and 50% S. pneumoniae bactericidal effects. Finally, the DES showed limited cytotoxic properties against human cell lines with the exception of the DES prepared from Methyltrioctylammonium chloride and Citric acid (DES-10), which had 88% cytotoxic effects. These findings suggest that DES depict potent antibacterial efficacies and cause minimal damage to human cells. It can be concluded that the selected DES in this study could be utilized as valuable and novel antibacterial drugs against bacterial infections. In future work, the mechanisms for bactericides and the cytotoxicity effects of these DES will be investigated.
在此,我们利用了几种基于氢供体和氢受体的深共晶溶剂(DES)来抗菌。测试了这些DES对革兰氏阳性(化脓性链球菌、蜡样芽孢杆菌、肺炎链球菌和耐甲氧西林金黄色葡萄球菌)和革兰氏阴性(大肠杆菌K1、肺炎克雷伯菌、铜绿假单胞菌和粘质沙雷氏菌)细菌的杀菌活性。采用乳酸脱氢酶测定,评价了DES对人细胞的细胞病变作用。抑菌试验结果表明,由甲基三辛基氯化铵与甘油(DES-4)组合制备的DES和由甲基三辛基氯化铵与果糖(DES-11)组合制备的DES在2µL剂量下具有广谱抗菌行为,且杀菌活性最高。DES-4对铜绿假单胞菌和大肠杆菌K1的抑菌活性分别为40%和68%。同样,DES-11分别消除了65%和61%的大肠杆菌K1和铜绿假单胞菌。在革兰氏阳性菌中,DES-4表现出重要的抗菌活性,对蜡样芽孢杆菌和肺炎链球菌的抑制作用分别为75%和51%。同样,DES-11描述了70%蜡样芽孢杆菌和50%肺炎链球菌的杀菌效果。最后,DES对人类细胞系的细胞毒作用有限,但由甲基三辛基氯化铵和柠檬酸(DES-10)制备的DES具有88%的细胞毒作用。这些发现表明,DES具有强大的抗菌功效,对人体细胞的损害最小。本研究筛选出的DES可作为有价值的新型抗细菌感染药物。在未来的工作中,我们将进一步研究这些杀菌剂的作用机制和它们的细胞毒性作用。
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引用次数: 5
Acknowledgment to the Reviewers of Scientia Pharmaceutica in 2022 感谢《科学制药》杂志2022年审稿人
IF 2.5 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-01-29 DOI: 10.3390/scipharm91010008
High-quality academic publishing is built on rigorous peer review [...]
高质量的学术出版建立在严格的同行评审的基础上[…]
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引用次数: 0
Phytochemical Characterization of Pterocephalus frutescens with In-Silico Evaluation as Chemotherapeutic Medicine and Oral Pharmacokinetics Prediction Study 蕨类植物化学特性、化学药物的计算机评价及口服药代动力学预测研究
IF 2.5 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-01-28 DOI: 10.3390/scipharm91010007
A. El-Hela, M. Bakr, Mostafa M. Hegazy, Mohammed A. Dahab, Ayman Abo Elmaaty, A. Ibrahim, Sami El Deeb, Hatem S. Abbass
Virtual screening of the potential lead chemotherapeutic phytochemicals from medicinal plants has useful application in the field of in-silico modelling and computer-based drug design by orienting and scoring ligands in the active binding site of a target protein. The phytochemical investigation of the Pterocephalus frutescens extract in n-butanol resulted in the isolation and structure elucidation of three iridoids and four flavonoids which were identified as Geniposide (1), Geniposidic acid (2), Nepetanudoside C (3), Isovitexin (4), Luteolin-7-O-glucoside (5) Isoorientin (6) and Orientin (7), respectively. Molecular docking studies were used to compare the binding energies of the isolated phytochemicals at four biological cancer-relevant targets; namely, aromatase, carbonic anhydrase IX, fatty acid synthase, and topoisomerase II-DNA complex. The docking study concluded that the isolated compounds have promising cytotoxic activities, in particular, Luteolin-7-O-glucoside (5) and Orientin (7) which exhibited high binding affinities among the isolated compounds at the active sites of the target enzymes; Aromatase (−8.73 Kcal/mol), and Carbonic anhydrase IX (−8.92 Kcal/mol), respectively, surpassing the corresponding binding scores of the co-crystallized ligands and the reference drugs at these target enzymes. Additionally, among the isolated compounds, Luteolin-7-O-glucoside (5) showed the most outstanding binding affinities at the active sites of the target enzymes; Fatty acid synthase, and Topisomerase II-DNA complex with binding scores of −6.82, and −7.99 Kcal/mol, respectively. Finally, the SwissADME online web tool predicted that most of these compounds possessed acceptable oral bioavailability and drug likeness characteristics.
通过定位和评分靶蛋白活性结合位点的配体,从药用植物中虚拟筛选潜在的先导化疗植物化学物质,在计算机建模和基于计算机的药物设计领域具有重要的应用。对正丁醇中翼头草提取物进行植物化学研究,分离并鉴定出3种环烯醚萜类化合物和4种黄酮类化合物,分别为京尼平苷(1)、京尼平苷酸(2)、Nepetanudoside C(3)、异牡荆素(4)、木犀草素-7- o -葡萄糖苷(5)、异荭草苷(6)和京尼平苷(7)。分子对接研究比较了分离的植物化学物质在4个癌症相关生物靶点上的结合能;即芳香化酶、碳酸酐酶IX、脂肪酸合成酶和拓扑异构酶II-DNA复合物。对接研究表明,分离得到的化合物具有较好的细胞毒活性,特别是木犀草素-7- o -葡萄糖苷(5)和荭草苷(7)在靶酶活性位点表现出较高的结合亲和力;芳香化酶(−8.73 Kcal/mol)和碳酸酐酶IX(−8.92 Kcal/mol),分别超过了这些共结晶配体和参考药物在这些靶酶上的相应结合分数。此外,在分离的化合物中,木犀草素-7- o -葡萄糖苷(5)在靶酶的活性位点上表现出最突出的结合亲和力;脂肪酸合成酶和Topisomerase II-DNA复合物的结合分数分别为- 6.82和- 7.99 Kcal/mol。最后,SwissADME在线网络工具预测,大多数这些化合物具有可接受的口服生物利用度和药物相似特性。
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引用次数: 2
A Review of the Biological Properties of Purple Corn (Zea mays L.) 紫玉米(Zea mays L.)生物学特性研究进展
IF 2.5 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-01-19 DOI: 10.3390/scipharm91010006
Heeyeon Kim, K. Lee, Minju Kim, M. Hong, P. Deepa, Songmun Kim
In the food and beverage industries, replacing synthetic colorants with plant-based colorants has become popular in recent times. Purple corn (Zea mays L.) is an important source of natural colorants due to its range in color from orange to purple. The whole plant of purple corn has a high amount of anthocyanin content. Anthocyanin is the water-soluble pigment found in various fruits and vegetables. The color pigments are chiefly found in the pericarp or kernels, in addition to corn cobs. Purple corn is rich in various health-promoting compounds, mainly anthocyanins such as cyanidin-3-O-glucoside, perlagonidin-3-O-glucoside, peonidin 3-O-glucoside, and their malonylated forms. This review emphasized recent updates regarding the in vitro and in vivo biological properties of extracts and compounds from purple corn. Purple corn color extracts possess a variety of biological properties, including antioxidant, anti-inflammatory, anticancer, anti-diabetic, anti-obesity, etc. The results of in vitro and in vivo studies of the biological properties of purple corn could lead to the development of different health-promoting products in the near future.
近年来,在食品和饮料行业,用植物性着色剂取代合成着色剂变得很流行。紫玉米(Zea mays L.)是天然着色剂的重要来源,因为它的颜色从橙色到紫色不等。紫玉米全株花青素含量较高。花青素是一种水溶性色素,存在于各种水果和蔬菜中。色素主要存在于果皮或玉米粒中,此外还有玉米芯。紫玉米富含各种有益健康的化合物,主要是花青素,如矢车菊素-3-O-葡萄糖苷、苝菁素-3-O-葡糖苷、牡丹素3-O-葡萄糖苷及其丙二酰化形式。这篇综述强调了紫玉米提取物和化合物的体外和体内生物学特性的最新进展。紫玉米色素提取物具有多种生物学特性,包括抗氧化、抗炎、抗癌、抗糖尿病、抗肥胖等。紫玉米生物学特性的体外和体内研究结果可能会在不久的将来开发出不同的健康促进产品。
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引用次数: 4
Detailing the Ten Main Professional Roles of a Pharmacist to Provide the Scope of Professional Functions 详述药剂师的十个主要专业角色以提供专业职能范围
IF 2.5 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-01-13 DOI: 10.3390/scipharm91010005
Yu. I. Kremin, L. Lesyk, R. Lesyk, O. Levytska, B. Hromovyk
As members of a public trust profession, pharmacists are the most accessible medical team members. Therefore, every pharmacist must know the scope of their professional roles (PR) and professional functions (PF). The study aimed to detail the major PR into a pooled set of PF. The research materials were the provisions of the World Health Organization, the International Pharmaceutical Federation, and scientific works on the PR of pharmacists. Methods of critical analysis, concretization, functional decomposition, and scientific generalization were used. As a result of detailing the 10 main PR according to the “ten-star pharmacist” concept for each, a combined set of partial PFs of the pharmacist was obtained. The decomposition takes into account the principle of complexity limitation, which allowed three to six partial PF for the respective PR to be obtained, namely: three PFs for a life-long-learner, five PFs for a caregiver, a decision-maker, a teacher, a leader, a researcher, an entrepreneur, and an agent of positive change, six PFs for a communicator and a manager. Thus, due to the decomposition of each of the 10 main PR of the pharmacist into three or six corresponding partial PFs, we received a multifunctional verbal model of difficult to organize, professional activities, which is identified by a total of 50 PFs. The importance of using this model in formulating professional competencies and learning outcomes of educational programs for pharmacists is emphasized.
作为公众信任职业的成员,药剂师是最容易接触到的医疗团队成员。因此,每个药剂师都必须知道自己的职业角色(PR)和职业职能(PF)的范围。这项研究旨在将主要的公共关系详细纳入一组PF。研究材料是世界卫生组织、国际制药联合会的规定,以及药剂师公共关系的科学著作。采用批判性分析法、具体化法、函数分解法和科学概括法。根据“十星级药剂师”的概念,详细说明了10个主要PR,从而获得了药剂师的部分PF的组合集。分解考虑了复杂性限制原则,该原则允许获得三到六个部分PF,用于相应的PR,即:终身学习者三个PF,护理者、决策者、教师、领导者、研究人员、企业家和积极变革推动者五个PF,沟通者和管理者六个PF。因此,由于药剂师的10个主要PR中的每一个都分解为三个或六个相应的部分PF,我们得到了一个难以组织的专业活动的多功能言语模型,共有50个PF。强调了使用该模型制定药剂师教育项目的专业能力和学习成果的重要性。
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引用次数: 0
Effectiveness of Platelet-Rich Plasma in the Treatment of Androgenic Alopecia Compared to Placebo and Topical Minoxidil: A Systematic Review 富血小板血浆治疗雄激素性脱发的有效性与安慰剂和局部米诺地尔的比较:一项系统综述
IF 2.5 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2022-12-31 DOI: 10.3390/scipharm91010004
Julia Maria Borowiecka, B. Dalewski, Ł. Pałka
Platelet-rich plasma (PRP) has become an increasingly popular alternative or additional method in treating androgenic alopecia (AGA). AGA is a multifactorial disease, in which testosterone plays a significant role in influencing hair growth. The aim of this study was to evaluate the effectiveness of PRP treatment in AGA affecting men and women. The research was performed using the following databases: PubMed, Embase, and Cochrane Library. The effects were measured with a TrichoScan by comparing the initial and final hair density. A significant difference was observed between the areas of the scalp where PRP injections were made and those where saline was administered. Compared to conventional minoxidil 5% topical PRP, PRP is more effective in treating alopecia. A beneficial outcome of combined therapy with PRP and minoxidil 5% was observed. Therefore, PRP is not only an excellent alternative for patients in whom the minoxidil 5% topical monotherapy did not bring the expected effects or who experienced unacceptable side effects, but can also be used as a complementary therapy.
富血小板血浆(PRP)已成为治疗雄激素性脱发(AGA)的一种日益流行的替代或附加方法。AGA是一种多因素疾病,其中睾酮在影响头发生长方面起着重要作用。本研究的目的是评估PRP治疗影响男性和女性AGA的有效性。本研究使用以下数据库进行:PubMed, Embase和Cochrane Library。通过比较初始和最终头发密度,用TrichoScan测量了效果。在注射PRP的头皮区域和注射生理盐水的头皮区域之间观察到显著的差异。与常规米诺地尔5%外用PRP相比,PRP治疗脱发更有效。PRP联合5%米诺地尔治疗效果良好。因此,PRP不仅是5%米诺地尔局部单药治疗未达到预期效果或出现不可接受副作用的患者的极好选择,而且可以作为补充治疗。
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引用次数: 0
Secondary Metabolites of Endophytes Associated with the Zingiberaceae Family and Their Pharmacological Activities 姜科内生植物的次生代谢产物及其药理活性
IF 2.5 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2022-12-23 DOI: 10.3390/scipharm91010003
Laita Nurjannah, A. Azhari, U. Supratman
Zingiberaceae is commonly known as the ginger family and has been extensively studied in the last decades for its pharmacological purposes. The study of ginger includes microorganisms known as endophytes, which raise interest for the research community because they can produce a wide range of secondary metabolites. This review discusses the secondary metabolites of endophytes from the Zingiberaceae family and their pharmacological activities. We detail the group of secondary metabolites, updated for its absolute structures, source and part origins, and, especially, pharmacological divided properties. Zingiberaceae endophytes have 106 volatile compounds and 52 isolated constituents, including 17 polyketides, five nonribosomal peptides, five aromatic compounds, three alkaloids, and 21 terpene-alkaloids. They have antimicrobial, anticancer, antioxidant, and anti-inflammatory activities. Secondary metabolites from plant endophytes of the Zingiberaceae family have the potential to be therapeutic drugs in the future. Research on endophytic bacteria or fungi has been little performed. Therefore, this study supports a new drug discovery from Zingiberaceae endophytes and compares them for future drug development.
姜科通常被称为姜科,在过去的几十年里,人们对其药理目的进行了广泛的研究。生姜的研究包括被称为内生菌的微生物,这引起了研究界的兴趣,因为它们可以产生广泛的次生代谢物。本文对姜科内生菌的次生代谢产物及其药理活性进行了综述。我们详细介绍了次生代谢物组,更新了其绝对结构,来源和部分来源,特别是药理学划分特性。姜科内生菌含有106种挥发性化合物和52种分离成分,包括17种多酮类化合物、5种非核糖体肽、5种芳香化合物、3种生物碱和21种萜烯类生物碱。它们具有抗菌、抗癌、抗氧化和抗炎活性。姜科植物内生菌的次生代谢物在未来具有开发治疗药物的潜力。对内生细菌或真菌的研究很少。因此,本研究为从姜科内生菌中发现新的药物提供了支持,并为将来的药物开发提供了比较。
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引用次数: 1
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Scientia Pharmaceutica
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