Metabolites Alkaloids Research Articles

Moringa oleifera and its Secondary Metabolites: Chemistry, Properties and Antidiabetic Potentiality

Abstract: Secondary metabolites present in different natural resources possess multiple biological activities. Diabetes is one of the leading disease all over the world in current time, and higher in numbersthan the deadliest cancer disease. According to the WHO about 422 million people are suffering from diabetes and most of them are even unaware that they are living with the condition. In recent times research in natural medicinal plants has achieved a great success in the management of different diseases and disorders. Moringa oleifera is one of the most common medicinal and nutritious plant among the family of moringaceae, found in almost all over India. The tree with it's almost every edible part makes it a versatile natural medicinal source. The secondary metabolites present within it make this plant a rich biological resource. Among various classes of secondary metabolites alkaloids, flavonoids, glycosides, terpenoids, sterols etc. are present in moringa tree. The principle potent compound responsible for emerging antidiabetic property of Moringa is 4-(α-Lrhamnopyranosyloxy) benzyl glucosinolate. In this review we summarise specifically the antidiabetic activity of this multipurpose natural plant and it's phytochemistry. Since ancient times this plant has been used as anti-diabetic agent in sub continental regions. Mostly phytoconstituents obtained from leaves are responsible for its outstanding antidiabetic property. Research on antidiabetic property of M. oleifera by different scientists proved that Moringa is one of the finest natural medicinal plants in the management of diabetes with least toxicity.

Insights into the Metabolite Profiles of Two Camellia (Theaceae) Species in Yunnan Province through Metabolomic and Transcriptomic Analysis.

Tea (Camellia sinensis) falls into the family Theaceae, is a valuable commercial crop, and tea products made from its buds and young leaves are favored by consumers all over the world. The more common Thea plant is Camellia sinensis (C. sinensis), but its most important relative, Camellia taliensis (C. taliensis), is also utilized by locals in the area of cultivation to manufacture tea. In this investigation, C. taliensis (DL) and C. sinensis (QJZ) were characterized in terms of their agronomic traits, physicochemical indices, metabolomics, and transcriptomics. The leaf area of DL is larger than that of QJZ; the color of DL's buds and leaves is yellowish-green, while that of QJZ's is green. DL's buds and leaves are more densely velvety than those of QJZ. The HPLC results indicated that the physicochemical contents varied considerably between the two samples, with DL having greater concentrations of EGCG and GABA than QJZ, while QJZ had remarkably higher concentrations of C, CA, and EGC than DL. A total of 2269 metabolites and 362,190,414 genes were positively identified, with the number of DAMs and DEGs being 1001 and 34,026, respectively. The flavonoids, phenolic acids, and alkaloid metabolites were dramatically different between the two tea group plants. Bioinformatics profiling revealed that the DAMs and DEGs of the two tea group plants interacted with each other and were involved in metabolic pathways, including "biosynthesis of secondary metabolites", "biosynthesis of amino acids", "biosynthesis of cofactors", "phenylpropanoid biosynthesis", and "flavonoid biosynthesis". Overall, these results provide statistical support for germplasm conservation and production for both C. taliensis and C. sinensis.

ANATOMICAL DEVELOPMENT AND HISTOCHEMICAL STUDY OF STERIL OVULE MELINJO (Gnetum gnemon L.)

In this section, the abstract must be written in English. Melinjo (Gnetum gnemon L.) is a plant that grows and spreads throughout Indonesia. This plant is widely cultivated because of its economic value. The purpose of this study was to determine the anatomical development of sterile melinjo ovule at the tip, middle and base of the female strobili and to determine the content of secondary metabolites in melinjo sterile ovule. The material used is sterile ovulum melinjo at the tip, middle and base of the female strobilus. In observing the anatomical development of sterile melinjo ovule, preparations were made using the paraffin method, single staining, and observed under a microscope. The anatomical data of the sterile ovule were analyzed descriptively. Observation of secondary metabolite content was carried out through histochemical tests, then observed with a light microscope and the results of the observations were documented using OptiLab. The results of observing anatomical development show that at different ages of melinjo sterile ovule there are structural differences in the constituent tissues. The results of observations on anatomical development show that at different ages the melinjo sterile ovule has structural differences in its constituent tissue, the more mature the melinjo sterile ovule, the constituent tissue is increasingly degraded. Histochemical test results showed that the sterile melinjo ovule contained secondary metabolites of phenols, flavonoids, terpenoids, tannins, and alkaloids.

Solid-state fermentation of Aspergillus sydowii G12, an approach to produce isocorydine

Isocorydine is an aporphine alkaloid that is mainly produced via chemical synthesis and extracted from plants. Its hydrochloride has been authorized to be a prescription drug for clinical use. This study aims to discover potential alkaloidal metabolites from endophytic fungi associated with the plant. Endophytic fungi were subjected to solid-state fermentation (SSF) to investigate the production of isocorydine. An aporphine alkaloid was obtained from the metabolite of SSF with Aspergillus sydowii G12. Its chemical structure was deduced to be isocorydine according to the spectroscopic data of ESI-MS, 1H and 13C NMR spectroscopy. The fermentation conditions including substrate, fermentation temperature, and time were optimized. As a result, SSF with A. sydowii G12 using potato as substrate at 20 °C for 15 d could produce isocorydine with a high yield of 2.51 ± 0.09 mg/g. This paper is the first to report an approach to producing isocorydine from microorganisms instead of plants.

Combined analysis of the metabolome and transcriptome reveals the metabolic characteristics and candidate genes involved in alkaloid metabolism in Heuchera micrantha Douglas ex Lindl

BackgroundAlkaloids, important secondary metabolites produced by plants, play a crucial role in responding to environmental stress. Heuchera micrantha, a well-known plant used in landscaping, has the ability to purify air, and absorb toxic and radioactive substances, showing strong environmental adaptability. However, there is still limited understanding of the accumulation characteristics and metabolic mechanism of alkaloids in H. micrantha.ResultsIn this study, four distinct varieties of H. micrantha were used to investigate the accumulation and metabolic traits of alkaloids in its leaves. We conducted a combined analysis of the plant’s metabolome and transcriptome. Our analysis identified 44 alkaloids metabolites in the leaves of the four H. micrantha varieties, with 26 showing different levels of accumulation among the groups. The HT and JQ varieties exhibited higher accumulation of differential alkaloid metabolites compared to YH and HY. We annotated the differential alkaloid metabolites to 22 metabolic pathways, including several alkaloid metabolism. Transcriptome data revealed 5064 differentially expressed genes involved in these metabolic pathways. Multivariate analysis showed that four key metabolites (N-hydroxytryptamine, L-tyramine, tryptamine, and 2-phenylethylamine) and three candidate genes (Cluster-15488.116815, Cluster-15488.146268, and Cluster-15488.173297) that merit further investigation.ConclusionsThis study provided preliminarily insight into the molecular mechanism of the biosynthesis of alkaloids in H. micrantha. However, further analysis is required to elucidate the specific regulatory mechanisms of the candidate gene involved in the synthesis of key alkaloid metabolites. In summary, our findings provide important information about how alkaloid metabolites build up and the metabolic pathways involved in H. micrantha varieties. This gives us a good starting point for future research on the regulation mechanism, and development, and utilization of alkaloids in H. micrantha.

Analgesic Activity Combination of Dry Extract of Meniran Leaves (Phyllanthus niruri L.) and Moringa Leaves (Moringa oleifera L.) Using the Chemical Induction Method: Invivo Study

Analgesics are drugs that selectively reduce pain in the central nervous system or peripheral pain mechanisms without significantly changing consciousness. This study aims to determine the analgesic activity of a combination of dry extracts of meniran leaves (Phyllanthus niruri l.) and moringa leaves (Moringa oleifera l.) against Swiss Webster rats with chemical induction methods. This research proves the presence of secondary metabolite content in the dry extract of meniran leaves and moringa leaves which have analgesic activity. The research used 30 male Swiss Webster rats divided into 5 groups. Group 1 is the negative control (CMC-Na 0.5%), group 2 is the positive control (diclofenac Na), group 3 (Dry extract of meniran leaves), group 4 (Dry extract of moringa leaves) and Group 5 (Combination of dry extracts). meniran and moringa leaves). Each was given 1 mL of 1% acetic acid induction chemical stimulation, then the writhing response was observed and recorded at 5-minute intervals for 30 minutes. The results showed that the K3 group combined dry extract of meniran leaves (Phyllanthus niruri L.) and moringa leaves (Moringa oleifera L) is not statistically significantly different from the positive control diclofenac sodium, p-value = 0.183. In conclusion, dry extract of meniran leaves (Phyllanthus niruri L.) and Moringa leaves (Moringa oleifera L.) has been proven to contain secondary metabolites of flavonoids, alkaloids, tannins, and saponins which have analgesic activity.

Metabolites rapid-annotation in mice by comprehensive method of virtual polygons and Kendric mass loss filtering: A case study of Dendrobium nobile Lindl

With significant advancements in high-resolution mass spectrometry, there has been a substantial increase in the amount of chemical component data acquired from natural products. Therefore, the rapid and efficient extraction of valuable mass spectral information from large volumes of high-resolution mass spectrometry data holds crucial significance. This study illustrates a targeted annotation of the metabolic products of alkaloid and sesquiterpene components from Dendrobium nobile (D. nobile) aqueous extract in mice serum through the integration of an in-houses database, R programming, a virtual metabolic product library, polygonal mass defect filtering, and Kendrick mass defect strategies. The research process involved initially establishing a library of alkaloids and sesquiterpenes components and simulating 71 potential metabolic reactions within the organism using R programming, thus creating a virtual metabolic product database. Subsequently, employing the virtual metabolic product library allowed for polygonal mass defect filtering, rapidly screening 1705 potential metabolites of alkaloids and 3044 potential metabolites of sesquiterpenes in the serum. Furthermore, based on the chemical composition database of D. nobile and online mass spectrometry databases, 95 compounds, including alkaloids, sesquiterpenes, and endogenous components, were characterized. Finally, utilizing Kendrick mass defect analysis in conjunction with known alkaloids and sesquiterpenes targeted screening of 209 demethylation, methylation, and oxidation products in phase I metabolism, and 146 glucuronidation and glutathione conjugation products in phase II metabolism. This study provides valuable insights for the rapid and accurate annotation of chemical components and their metabolites in vivo within natural products.

UJI EFEK EKSTRAK ETANOL UMBI TALAS HISTOPATOLOGI GINJAL TIKUS PUTIH JANTAN (Rattus norvegicus) DIINDUKSI STREPTOZOTOCIN

Diabetes mellitus is a systemic disease or metabolic syndrome caused by chronic disorders, especially in the body's carbohydrate, fat, and protein metabolism system. This study aims to determine the content of secondary metabolites of alkaloids, flavonoids, saponins, and tannins in the ethanolic extract of taro tubers and determine the effect and effective dose of the extract on the regeneration of kidney organ cells in streptozotocin-induced rats. Rats were divided into five groups: normal control, negative control, and extract treatment groups at doses of 100, 200, and 300 mg/kg BW that were performed for 28 days. This study observed changes that occurred in the renal tubular cells of white male rats induced by streptozotocin in the form of the level of damage with a value calculated based on the percentage (%) in each part of the tubule that was injured or damaged. The results showed that the taro tuber extract contained positive secondary metabolites of alkaloids, flavonoids, saponins, and tannins. Administration of ethanol extract of taro tubers at a dose of 300 mg/kg BW can affect the regeneration of kidney tubule cells in STZ-induced rats, with an average damage value of 1 out of a maximum of 4.

Comparative Analysis of the Gelsemium Alkaloids Metabolism in Human, Pig, Goat, and Rat Liver Microsomes.

The aim of this study was to investigate the metabolism of Gelsemium elegans in human, pig, goat and rat liver microsomes and to elucidate the metabolic pathways and cleavage patterns of the Gelsemium alkaloids among different species. A human, goat, pig and rat liver microsomes were incubated in vitro. After incubating at 37°C for 1 hour and centrifuging, the processed samples were detected by HPLC/Qq-TOFMS was used to detect alcohol extract of Gelsemium elegans and its metabolites. Forty-six natural products were characterized from alcohol extract of Gelsemium elegans and 13 metabolites were identified. These 13 metabolites belong to the gelsemine, koumine, gelsedine, humantenine, yohimbane, and sarpagine classes of alkaloids. The metabolic pathways included oxidation, demethylation and dehydrogenation. After preliminary identification, the metabolites detected in the four species were different. All 13 metabolites were detected in pig and rat microsomes, but no oxidative metabolites of Gelsedine-type alkaloids were detected in goat and human microsomes. In this study, Gelsemium elegans metabolic patterns in different species are clarified and the in vitro metabolism of Gelsemium elegans is investigated. It is of great significance for its clinical development and rational application.

ANTIOXIDANT ACTIVITY OF Homotrigona fimbriata PROPOLIS EXTRACT

Antioxidant compounds have a role in protecting the body from free radicals, Propolis from Homotrigona fimbriata species is widely used as an alternative to natural healing in East Kalimantan. The secondary metabolite compounds in propolis contain many flavonoids and phenolic compounds. These compounds can be utilized to fight free radicals. The purpose of this study was to determine the antioxidant content of stingless bee (Homotrigona fimbriata) propolis extract. This was a quantitative study of the antioxidant potential of propolis extract. The benchmark antioxidant activity was measured based on its ability to counteract free radicals using the DPPH method. The results of this study showed the presence of secondary metabolites of alkaloids, flavonoids, tannins, and saponins as well as antioxidant activity of Homotrigona fimbriata propolis extract with a value of 95,8 ppm as strong category. This can be caused by differences in geographical location, and various resins found in the trees around the beehive will affect antioxidant activity. Keywords: Homotrigona fimbriata, antioxidant, stingless bee

Transcriptomics and Metabolomics Reveal Tomato Consumption Alters Hepatic Xenobiotic Metabolism and Induces Steroidal Alkaloid Metabolite Accumulation in Mice.

Tomato consumption is associated with many health benefits including lowered risk for developing certain cancers. It is hypothesized that tomato phytochemicals are transported to the liver and other tissues where they alter gene expression in ways that lead to favorable health outcomes. However, the effects of tomato consumption on mammalian liver gene expression and chemical profile are not well defined. The study hypothesizes that tomato consumption would alter mouse liver transcriptomes and metabolomes compared to a control diet. C57BL/6J mice (n = 11-12/group) are fed a macronutrient matched diet containing either 10% red tomato, 10% tangerine tomato, or no tomato powder for 6 weeks after weaning. RNA-Seq followed by gene set enrichment analyses indicates that tomato type and consumption, in general, altered expression of phase I and II xenobiotic metabolism genes. Untargeted metabolomics experiments reveal distinct clustering between control and tomato fed animals. Nineteen molecular formulas (representing 75 chemical features) are identified or tentatively identified as steroidal alkaloids and isomers of their phase I and II metabolites; many of which are reported for the first time in mammals. These data together suggest tomato consumption may impart benefits partly through enhancing detoxification potential.

Comparative Metabolomics Revealed Differences in Alkaloids Metabolism Between Morus nigra L. and Morus. alba L. at Different Growth Stages

Mulberry (Morus spp.), a flowering plant in the Moraceae family, is known for the edible fruit, and mulberry leaves have various applications. This experiment utilized ultra-high performance liquid chromatography-quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS) and Progenesis QI software to rapidly identify secondary metabolites in the leaves of Morus nigra L. and Morus alba L.. Orthogonal partial least squares discriminant analysis (OPLS-DA), principal component analysis (PCA) and Hierarchical clustering analysis (HCA) were used to examine the dynamic changes and stage specificity of metabolites, particularly alkaloids, in M. nigra and M. alba leaves during seven primary growth stages. In results, the leaf samples from different growth stages uncovered a total of 182 metabolites from 13 distinct categories. M. nigra had significantly higher levels of metabolites than those in M. alba, according to differences in leaf metabolite accumulation patterns. Multiple statistical analyses revealed that the metabolome of M. nigra and M. alba leaves exhibited a significant interspecific and developmental specific accumulation patterns, with most DNJ alkaloids having the highest content in M. nigra leaves. In different growth stages, the metabolites of M. nigra leaves showed significant stage specificity. During the development stage of small fruit stage, obvious changes occurred in the chemical composition of M. nigra leaves, with a significant increase in DNJ alkaloid metabolites. Overall, this study provides a theoretical reference for the comprehensive development and sustainable utilization of M. nigra resources in Xinjiang.

Antibacterial Activity of Terminalia mantaly Stem Ethanol Extract as Hand Sanitizer Gel

Background: Hand sanitizers generally contain alcohol. However, it can cause dry and irritated skin. Therefore, it is necessary to find antibacterial alternatives that are safe for the skin. One of the plants that has antibacterial activity is Terminalia mantaly (T. mantaly). This study aimed to investigate the antibacterial activity of ethanol extract and hand sanitizer gel of T. mantaly.Methods: The antibacterial activity test against gram-positive (Staphylococcus aureus and Streptococcus pyogenes) and gram-negative bacteria (Escherichia coli and Shigella dysenteriae) was carried out using the liquid micro dilution method. The phytochemical tests were also performed. This study was conducted at the Chemistry Laboratory, Faculty of Sains and Informatics, Universitas Jenderal Achmad Yani in April-June 2022.Results: The ethanol extract of T. mantaly stem contained secondary metabolites of alkaloids, tannins, quinones, saponins, steroids, and flavonoids. The minimum inhibitory concentration (MIC) values of T. mantaly stem ethanol extract against Escherichia coli, Shigella dysenteriae, Staphylococcus aureus, Streptococcus pyogenes were 0.63%, 0.63%, 0.16%, and 0.16%, whereas the hand sanitizer gel gave MIC values of 0.63%; 0.31%; 0.16%; and 0.16% respectively. The minimum bactericidal concentration (MBC) values of T. mantaly stem ethanol extract and hand sanitizer gel had the same results, namely 2.50%, 0.16%, 1.25%, and 1.25%. The physical stability of the hand sanitizer gel from the ethanol extract of T. mantaly stem met the physical stability standards of the gel. Conclusions: The ethanol extract of the T. mantaly stems has stronger antibacterial activity against gram-positive bacteria than against gram- negative bacteria.

Antioxidant Activity and Toxicity Tests of Panahan Leaf Extract (Ayapana triplinervis (Vahl) RM) against Shrimp Larvae ( Artemia salina Leach)

Research on the antioxidant activity test and toxicity test of leaf extract (Ayapana triplinervis (ValH) RM) has been conducted against the larval shrimp (Artemia salina Leach). The dried leaves weighing 500 grams were macerated using methanol, filtered, and concentrated using a rotary evaporator. Methanol crude extract was fractionated with n-hexane, ethyl acetate, and methanol water. Based on Test Phytochemicals screening on secondary metabolites showed that the crude extract of methanol, n-hexane fraction, and methanol-water containing secondary metabolites alkaloids, flavonoids, and phenolic in ethyl acetate fraction of the content of secondary metabolites, alkaloids, and flavonoids, and the fraction of n-hexane and ethyl acetate contain steroids. In contrast, the crude extract of methanol and n-hexane fraction contains phenolic compounds. Test mortality of shrimp larvae (Brine Shrimp Lethality Test) showed mortality of shrimp larvae (Artemia salina Leach) using Probit analysis (SAS) to determine the value of 50% Lethal Concentration (LC50). In this test, the most active is the methanol crude extract of archery leaves, with a value of 18.8608 ppm, in a test of antioxidant activity using DPPH free radical reduction in the spectrophotometer and IC50 values obtained. In methanol crude extract was 430.73 ppm; n-hexane fraction was 168.5 ppm; ethyl acetate fraction was 114.87 ppm; and methanol-water fraction was 37.23 ppm

The Effect of Binahong Leaves (Anredera cordifolia Steenis) Extract on Blood Urea Nitrogen (BUN) Creatinine Serum and Renal Histopathology of Male White Rats (Rattus norvegicus) with Diabetes Mellitus

Diabetic nephropathy is one of the complications of diabetes mellitus on the pancreas that can end up in chronic pancreas failure. Various treatment options to repair pancreas damage due to diabetic nephropathy, one of which is by using Anredera cordifolia leaves. This study aims to determine the content of secondary metabolites in Anredera cordifolia leaves ethanol extract, and to determine the effective dose of Anredera cordifolia leaves ethanol extract in regenerating male white rat kidney cells. This study uses a laboratory experimental method. This study used 30 rats divided into 6 treatment groups, each group consisting of 5 test animals, namely normal group, negative control, positive control, dose of 25 mg/kg BW, dose 50 mg/kg BW, and dose 100 mg/kg bw. The level of histological damage to the renal tubules was observed with HE staining using an Olympus CX23 microscope. The data from the scoring of the level of renal tubular damage were analyzed using the Kruskal-Wallis test followed by the Mann-Whitney test to see the differences between treatments. The results showed that the Anredera cordifolia leaves ethanol extract contained secondary metabolites of alkaloids, flavonoids, saponins, and tannins; Anredera cordifolia leaves ethanol extract has an effect on kidney cell repair; Anredera cordifolia leaves ethanol extract at a dose of 100 mg/kg bw is effective reducing urea and creatinine; with an average decrease of 17.0 and 0.71 mg/dL in repairing kidney cells with an average damage value of 1.

Influence of Half-life and Smoking/Nonsmoking Ratio on Biomarker Consistency between Waves 1 and 2 of the Population Assessment of Tobacco and Health Study.

Biomarkers of exposure are tools for understanding the impact of tobacco use on health outcomes if confounders like demographics, use behavior, biological half-life, and other sources of exposure are accounted for in the analysis. We performed multiple regression analysis of longitudinal measures of urinary biomarkers of alkaloids, tobacco-specific nitrosamines, polycyclic aromatic hydrocarbons, volatile organic compounds (VOC), and metals to examine the sample-to-sample consistency in Waves 1 and 2 of the Population Assessment of Tobacco and Health (PATH) Study including demographic characteristics and use behavior variables of persons who smoked exclusively. Regression coefficients, within- and between-person variance, and intra-class correlation coefficients (ICC) were compared with biomarker smoking/nonsmoking population mean ratios and biological half-lives. Most biomarkers were similarly associated with sex, age, race/ethnicity, and product use behavior. The biomarkers with larger smoking/nonsmoking population mean ratios had greater regression coefficients related to recency of exposure. For VOC and alkaloid metabolites, longer biological half-life was associated with lower within-person variance. For each chemical class studied, there were biomarkers that demonstrated good ICCs. For most of the biomarkers of exposure reported in the PATH Study, for people who smoke cigarettes exclusively, associations are similar between urinary biomarkers of exposure and demographic and use behavior covariates. Biomarkers of exposure within-subject consistency is likely associated with nontobacco sources of exposure and biological half-life. Biomarkers measured in the PATH Study provide consistent sample-to-sample measures from which to investigate the association of adverse health outcomes with the characteristics of cigarettes and their use.

Elucidating the Differentiation Synthesis Mechanisms of Differently Colored Resistance Quinoa Seedings Using Metabolite Profiling and Transcriptome Analysis.

Quinoa (Chenopodium quinoa wild.), a dicotyledonous plant native to the Andes, is an increasingly popular pseudograin owing to its high nutritional value, stress resistance capabilities, and gluten-free properties. In this study, we aimed to explore the dynamic changes in different varieties of quinoa at the seedling stage and their regulatory networks. Here, we found that the leaves of quinoa showed obvious coloration after 45 days, and four quinoa seedling types (red, white, yellow, and black) were subjected to ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and transcriptome sequencing to identify their differentially expressed genes and metabolites. A total of 29 differential metabolites and 19 genes (14 structural and 5 regulatory genes) were identified, and consistent differences were observed in the flavonoid, phenolic acid, and alkaloid metabolites in the different quinoa types. These differential metabolites were significantly enriched in flavonoid and flavonol biosynthesis, flavonoid biosynthesis, and phenylpropanoid biosynthesis pathways. In addition, real-time fluorescence quantitative PCR (RT-qPCR) technology was used to detect the expression of four structural genes involved in the flavonoid biosynthesis pathway and four regulatory genes (interaction network). The results revealed that the structural and regulatory gene transcript levels in the flavonoid pathway were higher in the red quinoa cultivars than in the white, yellow, and black. Additionally, the differences in the leaves of these four quinoa cultivars were mainly due to differences in flavonoid, phenolic acid, and alkaloid accumulation. Our findings provide a basis for understanding the accumulation and coloration mechanisms of flavonoids, phenolic acids, and alkaloids in quinoa seedlings of different colors and also provide a theoretical basis for future investigations.

Exploration of the main active metabolites from Tinospora crispa (L.) Hook. f. & Thomson stem as insulin sensitizer in L6.C11 skeletal muscle cell by integrating in vitro, metabolomics, and molecular docking

Ethnopharmacological relevanceTinospora crispa (L.) Hook. f. & Thomson stem (TCS) has long been used as folk medicine for the treatment of diabetes mellitus. Previous study revealed that TCS possesses multi-ingredients and multi-targets characteristic potential as insulin sensitizer activity. However, its mechanisms of action and molecular targets are still obscure. Aim of the studyIn the present study, we investigated the effects of TCS against insulin resistance in muscle cells through integrating in vitro experiment and identifying its active biomarker using metabolomics and in molecular docking validation. Materials and methodsWe used centrifugal partition chromatography (CPC) to isolate 33 fractions from methanolic extract of TCS, and then used UHPLC-Orbitrap-HRMS to identify the detectable metabolites in each fraction. We assessed the insulin sensitization activity of each fraction using enzyme-linked immunosorbent assay (ELISA), and then used confocal immunocytochemistry microscopy to measure the translocation of glucose transporter 4 (GLUT4) to the cell membrane. The identified active metabolites were further simulated for its molecular docking interaction using Autodock Tools. ResultsThe polar fractions of TCS significantly increased insulin sensitivity, as measured by the inhibition of phosphorylated insulin receptor substrate-1 (pIRS1) at serine-312 residue (ser312) also the increasing number of translocated GLUT4 and glycogen content. We identified 58 metabolites of TCS, including glycosides, flavonoids, alkaloids, coumarins, and nucleotides groups. The metabolomics and molecular docking simulations showed the presence of minor metabolites consisting of tinoscorside D, higenamine, and tinoscorside A as the active compounds. ConclusionsOur findings suggest that TCS is a promising new treatment for insulin resistance and the identification of the active metabolites in TCS could lead to the development of new drugs therapies for diabetes that target these pathways.

Metabolomics and transcriptomics analyses for characterizing the alkaloid metabolism of Chinese jujube and sour jujube fruits.

Jujube is an important economic forest tree whose fruit is rich in alkaloids. Chinese jujube (Ziziphus jujuba Mill.) and sour jujube (Ziziphus spinosa Hu.) are the two most important species of the jujube genus. However, the mechanisms underlying the synthesis and metabolism of alkaloids in jujube fruits remain poorly understood. In this study, the fruits of Ziziphus jujuba 'Hupingzao' and Ziziphus spinosa 'Taigusuanzao' in different harvest stages were used as test materials, we first integrated widely targeted metabolomics and transcriptomics analyses to elucidate the metabolism of alkaloids of jujube fruits. In the metabolomics analysis, 44 alkaloid metabolites were identified in 4 samples, 3 of which were unique to sour jujube fruit. The differential alkaloid metabolites (DAMs) were more accumulated in sour jujube than in Chinese jujube; further, they were more accumulated in the white ripening stage than in the red stage. DAMs were annotated to 12 metabolic pathways. Additionally, transcriptomics data revealed 259 differentially expressed genes (DEGs) involved in alkaloid synthesis and metabolism. By mapping the regulatory networks of DAMs and DEGs, we screened out important metabolites and 11 candidate genes. This study preliminarily elucidated the molecular mechanism of jujube alkaloid synthesis. The candidate genes regulated the synthesis of key alkaloid metabolites, but the specific regulation mechanism is unclear. Taken together, our results provide insights into the metabolic networks of alkaloid synthesis in Chinese jujube and sour jujube fruits at different harvest stages, thereby providing a theoretical reference for further research on the regulatory mechanism of jujube alkaloids and their development and utilization.

Structures and Biological Activities of Secondary Metabolites from the Trichoderma genus (Covering 2018-2022).

Trichoderma, a genus with more than 400 species, has a long history of use as an industrial bioreactor, biofertilizer, and biocontrol agent. It is considered a significant source of secondary metabolites (SMs) that possess unique structural features and a wide range of bioactivities. In recent years, numerous secondary metabolites of Trichoderma, including terpenoids, polyketides, peptides, alkaloids, and steroids, have been identified. Most of these SMs displayed antimicrobial, cytotoxic, and antifungal effects. This review focuses on the structural diversity, biological activities, and structure-activity relationships (SARs) of the SMs isolated from Trichoderma covered from 2018 to 2022. This study provides insights into the exploration and utilization of bioactive compounds from Trichoderma species in the agriculture or pharmaceutical industry.