天然单萜柠檬烯的微生物转化

天然单萜柠檬烯资源丰富,价格便宜,在日用化工和医药行业已得到重要的应用。近几十年来,以柠檬烯为起始原料的新产品的研究与开发一直受到关注。大量文献报道了微生物能够对柠檬烯进行生物转化,得到系列在化妆品、食品、医药、有机合成等领域有重要应用价值的含氧衍生物。本文系统地综述了柠檬烯的微生物转化菌株和所得到转化产物的结构,分析了微生物对柠檬烯的主要转化途径以及影响微生物转化效率的主要因素。柠檬烯经微生物转化所得到的产物具有区域和立体选择性,并且难以通过人工合成方法得到。对生物转化过程进行系统优化,将有可能实现有用化合物的工业化生产。此外,在转化过程中诱导的高活性酶,尤其是单加氧酶和羟化酶的研究与应用也展现了诱人的前景。     

Limonene as an agro-chemical building block for the synthesis and extraction of bioactive compounds

The objective of this study was to transform limonene as an agro-chemical platform for the production of a wide range of added-value compounds for pharmaceutical, cosmetic and food ingredients. This molecule was also evaluated as an alternative solvent for the extraction of several bioactive compounds compared to n-hexane. Limonene was extracted from the essential oils of orange peels through a solvent-free microwave extraction technique. Limonene was successfully transformed into products with industrial interest by catalytic oxidation using three different iron catalysts. The ability of limonene to be used as an alternative solvent was performed using two simulation tools, Hansen solubility parameters (HSPs) and the Conductor-like Screening Model for Real Solvents (COSMO-RS), and via experimentation. The results indicated that limonene could be a promising green solvent and synthon for petroleum substitution in the extraction or synthesis of bioactive compounds.     

柠檬烯和柠檬烯氧化物与硫酸的非均相反应动力学

主要对天然挥发性有机物柠檬烯和柠檬烯氧化物在30%-80% (w)硫酸表面的非均相吸收反应进行了研究, 借以评估天然挥发性有机物与大气环境中的酸性气溶胶的反应活性. 采用自行搭建的配以单光子激光电离飞行时间质谱的湿壁流动反应管的设备对柠檬烯及其氧化物在硫酸表面的非均相吸收动力学进行了测定,计算了稳态摄取系数(γ). 实验结果表明, 柠檬烯氧化物在硫酸表面比只含有双键的柠檬烯的反应活性高, 室温下柠檬烯氧化物在30%-50% (w)硫酸上对应的稳态摄取系数是(7.100±0.023)×10^-5-(8.150±0.162)×10^-3. 此外, 还利用气相色谱-质谱(GC-MS)联用和电喷雾电离质谱(ESI-MS)对柠檬烯氧化物与硫酸的体相反应产物进行了研究, 产物包括单萜烯、松油醇、水合萜二醇和水合萜二醇二硫酸酯. 其中, 水合萜二醇二硫酸酯作为有机硫酸酯的一种, 能够改变气溶胶的吸湿性, 增强云凝结核的活性, 对于大气中灰霾的形成可能有明显的促进作用.     

Efficient Approach for the Synthesis of Novel Functionalized Isoxazolines from Limonene

New functionalized isoxazolines were effeciently and easily prepared from limonene. The procedure involves a peri‐ and regioselective 1,3‐dipolar cycloaddition of nitrile oxides on the monoterpene external double bond, followed by a highly chemoselective RuCl₃‐NaIO₄ oxidative cleavage of the internal one. All the newly prepared isoxazolyl‐ketoacids were fully characterized from their spectroscopic data.     

Green Tea Catechins Attenuate Neurodegenerative Diseases and Cognitive Deficits

Neurodegenerative diseases exert an overwhelming socioeconomic burden all around the globe. They are mainly characterized by modified protein accumulation that might trigger various biological responses, including oxidative stress, inflammation, regulation of signaling pathways, and excitotoxicity. These disorders have been widely studied during the last decade in the hopes of developing symptom-oriented therapeutics. However, no definitive cure has yet been discovered. Tea is one of the world’s most popular beverages. The same plant, Camellia Sinensis (L.).O. Kuntze, is used to make green, black, and oolong teas. Green tea has been most thoroughly studied because of its anti-cancer, anti-obesity, antidiabetic, anti-inflammatory, and neuroprotective properties. The beneficial effect of consumption of tea on neurodegenerative disorders has been reported in several human interventional and observational studies. The polyphenolic compounds found in green tea, known as catechins, have been demonstrated to have many therapeutic effects. They can help in preventing and, somehow, treating neurodegenerative diseases. Catechins show anti-inflammatory as well as antioxidant effects via blocking cytokines’ excessive production and inflammatory pathways, as well as chelating metal ions and free radical scavenging. They may inhibit tau protein phosphorylation, amyloid beta aggregation, and release of apoptotic proteins. They can also lower alpha-synuclein levels and boost dopamine levels. All these factors have the potential to affect neurodegenerative disorders. This review will examine catechins’ neuroprotective effects by highlighting their biological, pharmacological, antioxidant, and metal chelation abilities, with a focus on their ability to activate diverse cellular pathways in the brain. This review also points out the mechanisms of catechins in various neurodegenerative and cognitive diseases, including Alzheimer’s, Parkinson’s, multiple sclerosis, and cognitive deficit.     

Menthatrienes and the Oxidation of Limonene

The oxidation of limonene with mercuric acetate gives a mixture containing mentha-1. 3. 8-triene, the hydrocarbon of parsley, and its isomer, mentha-1. 4. 8-triene. Selenium dioxide oxidation of limonene in alcohol gives as the main product mentha-1. 8-dien-4-ol, and pyrolysis of the acetate of the latter, or of mentha-1. 8-dien-10-yl acetate (the main product of the oxidation of limonene with selenium dioxide in acetic anhydride), also gives a mixture of menthatrienes. A discussion of the selenium dioxide oxidation of limonene is presented.     

Conifers Phytochemicals: A Valuable Forest with Therapeutic Potential

Conifers have long been recognized for their therapeutic potential in different disorders. Alkaloids, terpenes and polyphenols are the most abundant naturally occurring phytochemicals in these plants. Here, we provide an overview of the phytochemistry and related commercial products obtained from conifers. The pharmacological actions of different phytochemicals present in conifers against bacterial and fungal infections, cancer, diabetes and cardiovascular diseases are also reviewed. Data obtained from experimental and clinical studies performed to date clearly underline that such compounds exert promising antioxidant effects, being able to inhibit cell damage, cancer growth, inflammation and the onset of neurodegenerative diseases. Therefore, an attempt has been made with the intent to highlight the importance of conifer-derived extracts for pharmacological purposes, with the support of relevant in vitro and in vivo experimental data. In short, this review comprehends the information published to date related to conifers’ phytochemicals and illustrates their potential role as drugs.     

A Narrative Review on the Phytochemistry,Pharmacology and Therapeutic Potentials of Clinacanthus nutans (Burm. f.) Lindau Leaves as an Alternative Source of Future Medicine

The application of natural products and supplements has expanded tremendously over the past few decades. Clinacanthus nutans (C. nutans), which is affiliated to the Acanthaceae family, has recently caught the interest of researchers from the countries of subtropical Asia due to its medicinal uses in alternative treatment for skin infection conditions due to insect bites, microorganism infections and cancer, as well as for health well-being. A number of bioactive compounds from this plant’s extract, namely phenolic compounds, sulphur containing compounds, sulphur containing glycosides compounds, terpens-tripenoids, terpens-phytosterols and chlorophyll-related compounds possess high antioxidant activities. This literature search yielded about one hundred articles which were then further documented, including the valuable data and findings obtained from all accessible electronic searches and library databases. The promising pharmacological activities from C. nutans leaves extract, including antioxidant, anti-cancer, anti-viral, anti-bacterial, anti-fungal, anti-venom, analgesic and anti-nociceptive properties were meticulously dissected. Moreover, the authors also discuss a few of the pharmacological aspect of C. nutans leaves extracts against anti-hyperlipidemia, vasorelaxation and renoprotective activities, which are seldom available from the previously discussed review papers. From the aspect of toxicological studies, controversial findings have been reported in both in-vitro and in-vivo experiments. Thus, further investigations on their phytochemical compounds and their mode of action showing pharmacological activities are required to fully grasp both traditional usage and their suitability for future drugs development. Data related to therapeutic activity and the constituents of C. nutans leaves were searched by using the search engines Google scholar, PubMed, Scopus and Science Direct, and accepting literature reported between 2010 to present. On the whole, this review paper compiles all the available contemporary data from this subtropical herb on its phytochemistry and pharmacological activities with a view towards garnering further interest in exploring its use in cardiovascular and renal diseases.     

The Therapeutic Potential of Celastrol in Central Nervous System Disorders: Highlights from In Vitro and In Vivo Approaches

Celastrol, the most abundant compound derived from the root of Tripterygium wilfordii, largely used in traditional Chinese medicine, has shown preclinical and clinical efficacy for a broad range of disorders, acting via numerous mechanisms, including the induction of the expression of several neuroprotective factors, the inhibition of cellular apoptosis, and the decrease of reactive oxygen species (ROS). Given the crucial implication of these pathways in the pathogenesis of Central Nervous System disorders, both in vitro and in vivo studies have focused their attention on the possible use of this compound in these diseases. However, although most of the available studies have reported significant neuroprotective effects of celastrol in cellular and animal models of these pathological conditions, some of these data could not be replicated. This review aims to discuss current in vitro and in vivo lines of evidence on the therapeutic potential of celastrol in neurodegenerative diseases, including Alzheimer’s and Parkinson’s diseases, amyotrophic lateral sclerosis, Huntington’s disease, multiple sclerosis, and cadmium-induced neurodegeneration, as well as in psychiatric disorders, such as psychosis and depression. In vitro and in vivo studies focused on celastrol effects in cerebral ischemia, ischemic stroke, traumatic brain injury, and epilepsy are also described.     

Study of Ozone-Initiated Limonene Reaction Products by Low Temperature Plasma Ionization Mass Spectrometry

Limonene and its ozone-initiated reaction products were investigated in situ by low temperature plasma (LTP) ionization quadrupole time-of-flight (QTOF) mass spectrometry. Helium was used as discharge gas and the protruding plasma generated ~850 ppb ozone in front of the glass tube by reaction with the ambient oxygen. Limonene applied to filter paper was placed in front of the LTP afterglow and the MS inlet. Instantly, a wide range of reaction products appeared, ranging from m/z 139 to ca. 1000 in the positive mode and m/z 115 to ca. 600 in the negative mode. Key monomeric oxidation products including levulinic acid, 4-acetyl-1-methylcyclohexene, limonene oxide, 3-isopropenyl-6-oxo-heptanal, and the secondary ozonide of limonene could be identified by collision-induced dissociation. Oligomeric products ranged from the nonoxidized dimer of limonene (C₂₀H₃₀) and up to the hexamer with 10 oxygen atoms (C₆₀H₉₀O₁₀). The use of LTP for in situ ozonolysis and ionization represents a new and versatile approach for the assessment of ozone-initiated terpene chemistry.

Development of neurotrophic molecules for treatment of neurodegeneration

Over the past several years, neurotrophic factors have made considerable progress from the laboratory into the clinic. Evidence from preclinical and clinical studies indicates that it may be possible to use neurotrophic factors to prevent, slow the progression of, or even reverse the effects of a number of neurodegenerative diseases and other types of insults in both the central and peripheral nervous system. Their potential importance in the development of therapeutic agents against neurodegenerative disorders and nerve injury has led to a flurry of activity towards understanding their structure, function and signalling mechanisms. Approaches to develop pharmacological agents that target neurotrophic factors, their receptors or neurotrophic factors signalling pathways have been attempted. This review focuses on some of the major themes and lines of mechanistic and therapeutic advances in this fast-moving field of neuroscience.     

Natural and Nature-Derived Products Targeting Human Coronaviruses

The ongoing pandemic of severe acute respiratory syndrome (SARS), caused by the SARS-CoV-2 human coronavirus (HCoV), has brought the international scientific community before a state of emergency that needs to be addressed with intensive research for the discovery of pharmacological agents with antiviral activity. Potential antiviral natural products (NPs) have been discovered from plants of the global biodiversity, including extracts, compounds and categories of compounds with activity against several viruses of the respiratory tract such as HCoVs. However, the scarcity of natural products (NPs) and small-molecules (SMs) used as antiviral agents, especially for HCoVs, is notable. This is a review of 203 publications, which were selected using PubMed/MEDLINE, Web of Science, Scopus, and Google Scholar, evaluates the available literature since the discovery of the first human coronavirus in the 1960s; it summarizes important aspects of structure, function, and therapeutic targeting of HCoVs as well as NPs (19 total plant extracts and 204 isolated or semi-synthesized pure compounds) with anti-HCoV activity targeting viral and non-viral proteins, while focusing on the advances on the discovery of NPs with anti-SARS-CoV-2 activity, and providing a critical perspective.     

Targeting Monoacylglycerol Lipase in Pursuit of Therapies for Neurological and Neurodegenerative Diseases

Neurological and neurodegenerative diseases are debilitating conditions, and frequently lack an effective treatment. Monoacylglycerol lipase (MAGL) is a key enzyme involved in the metabolism of 2-AG (2-arachidonoylglycerol), a neuroprotective endocannabinoid intimately linked to the generation of pro- and anti-inflammatory molecules. Consequently, synthesizing selective MAGL inhibitors has become a focus point in drug design and development. The purpose of this review was to summarize the diverse synthetic scaffolds of MAGL inhibitors concerning their potency, mechanisms of action and potential therapeutic applications, focusing on the results of studies published in the past five years. The main irreversible inhibitors identified were derivatives of hexafluoroisopropyl alcohol carbamates, glycol carbamates, azetidone triazole ureas and benzisothiazolinone, whereas the most promising reversible inhibitors were derivatives of salicylketoxime, piperidine, pyrrolidone and azetidinyl amides. We reviewed the results of in-depth chemical, mechanistic and computational studies on MAGL inhibitors, in addition to the results of in vitro findings concerning selectivity and potency of inhibitors, using the half maximal inhibitory concentration (IC₅₀) as an indicator of their effect on MAGL. Further, for highlighting the potential usefulness of highly selective and effective inhibitors, we examined the preclinical in vivo reports regarding the promising therapeutic applications of MAGL pharmacological inhibition.     

Biotechnological Innovations from Ocean: Transpiring Role of Marine Drugs in Management of Chronic Disorders

Marine drugs are abundant in number, comprise of a diverse range of structures with corresponding mechanisms of action, and hold promise for the discovery of new and better treatment approaches for the management of several chronic diseases. There are huge reserves of natural marine biological compounds, as 70 percent of the Earth is covered with oceans, indicating a diversity of chemical entities on the planet. The marine ecosystems are a rich source of bioactive products and have been explored for lead drug molecules that have proven to be novel therapeutic targets. Over the last 70 years, many structurally diverse drug products and their secondary metabolites have been isolated from marine sources. The drugs obtained from marine sources have displayed an exceptional potential in the management of a wide array of diseases, ranging from acute to chronic conditions. A beneficial role of marine drugs in human health has been recently proposed. The current review highlights various marine drugs and their compounds and role in the management of chronic diseases such as cancer, diabetes, neurodegenerative diseases, and cardiovascular disorders, which has led to the development of new drug treatment approaches.     

Mn-SOD模拟物及其在神经退行性疾病中的药用前景

本文通过分析神经退行性疾病与线粒体机能障碍、自由基损伤的关系,主要讨论了Mn-SOD模拟物作为自由基清除剂对活性氧化合物的清除机理、药用优势,并总结了近年来有关Mn-SOD模拟物在神经退行性疾病防治方面的研究近况及潜在应用前景。     

Alzheimer’s Disease,Cholesterol, and Statins: The Junctions of Important Metabolic Pathways

Recent years have seen a significant increase in published data supporting the positive effects of statins on neurodegenerative diseases, in particular on Alzheimer’s disease. Statins show neuroprotective activity by a combination of different cellular and systemic mechanisms that are based on the inhibition of the biosynthesis of cholesterol and isoprenoid by‐products. The promising results obtained in vivo and in epidemiological studies are generally not in accordance with those of placebo‐controlled randomized clinical trials. Nevertheless, these results make statins valuable assets for disease prevention rather than therapeutic agents for use when disease symptoms are already displayed. Thus, the modulation of midlife cholesterol and/or statin administration prior to the appearance of dementia or cognitive impairment may have a better long‐term outcome.     

Zebrafish: A Pharmacological Model for Learning and Memory Research

Learning and memory are essential to organism survival and are conserved across various species, especially vertebrates. Cognitive studies involving learning and memory require using appropriate model organisms to translate relevant findings to humans. Zebrafish are becoming increasingly popular as one of the animal models for neurodegenerative diseases due to their low maintenance cost, prolific nature and amenability to genetic manipulation. More importantly, zebrafish exhibit a repertoire of neurobehaviors comparable to humans. In this review, we discuss the forms of learning and memory abilities in zebrafish and the tests used to evaluate the neurobehaviors in this species. In addition, the pharmacological studies that used zebrafish as models to screen for the effects of neuroprotective and neurotoxic compounds on cognitive performance will be summarized here. Lastly, we discuss the challenges and perspectives in establishing zebrafish as a robust model for cognitive research involving learning and memory. Zebrafish are becoming an indispensable model in learning and memory research for screening neuroprotective agents against cognitive impairment.     

Natural and Synthetic Agents Targeting Reactive Carbonyl Species against Metabolic Syndrome

Reactive carbonyl species (RCS) may originate from the oxidation of unsaturated fatty acids and sugar in conditions of pathology. They are known to have high reactivity towards DNA as well as nucleophilic sites of proteins, resulting in cellular dysfunction. It has been considered that various pathological conditions are associated with an increased level of RCS and their reaction products. Thus, regulating the levels of RCS may be associated with the mitigation of various metabolic and neurodegenerative disorders. In order to perform a comprehensive review, various literature databases, including MEDLINE, EMBASE, along with Google Scholar, were utilized to obtain relevant articles. The voluminous review concluded that various synthetic and natural agents are available or in pipeline research that hold tremendous potential to be used as a drug of choice in the therapeutic management of metabolic syndrome, including obesity, dyslipidemia, diabetes, and diabetes-associated complications of atherosclerosis, neuropathy, and nephropathy. From the available data, it may be emphasized that various synthetic agents, such as carnosine and simvastatin, and natural agents, such as polyphenols and terpenoids, can become a drug of choice in the therapeutic management for combating metabolic syndromes that involve RCS in their pathophysiology. Since the RCS are known to regulate the biological processes, future research warrants detailed investigations to decipher the precise mechanism.     

Origanum syriacum Phytochemistry and Pharmacological Properties: A Comprehensive Review

Herbal medicine has been gaining special interest as an alternative choice of treatment for several diseases, being generally accessible, cost-effective and safe, with fewer side-effects compared to chemically synthesized medicines. Over 25% of drugs worldwide are derived from plants, and surveys have shown that, when available, herbal medicine is the preferred choice of treatment. Origanum syriacum (Lamiaceae) is a widely used medicinal plant in the Middle East, both as a home and a folk remedy, and in the food and beverage industry. Origanum syriacum contains numerous phytochemical compounds, including flavonoids, phenols, essential oils, and many others. Because of its bioactive compounds, O. syriacum possesses antioxidant, antimicrobial, and antiparasitic capacities. In addition, it can be beneficial in the treatment of various diseases such as cancer, neurodegenerative disorders, and peptic ulcers. In this review, the chemical compositions of different types of extracts and essential oils from this herb will first be specified. Then, the pharmacological uses of these extracts and essential oils in various contexts and diseases will be discussed, putting emphasis on their efficacy and safety. Finally, the cellular and molecular mechanisms of O. syriacum phytochemicals in disease treatment will be described as a basis for further investigation into the plant’s pharmacological role.