Dynamic Changes of Endogenic or Exogenic β-Carboline Alkaloid Harmine in Different Mammals and Human in vivo at Developmental and Physiological States

ObjectiveSeveral β-carboline alkaloids (βCBs), such as harmine, harmaline, harmane, and nor-harmane, are effective for Alzheimer’s disease mouse models. They can be found in some plants, common foodstuffs, and blank plasma of various mammals. However, whether these compounds in mammals are exogenous or endogenous remain unclear.MethodsThe exposure levels of βCBs and of neurotransmitters in plasma and tissues of pup rats, aging rats, mice of different physiological states, and healthy volunteers were detected by using UPLC-MS/MS. Plasma and tissue samples from 110 newborn rats up to 29 days old at 11 sampling points were collected and were analyzed to determine the concentration variation of βCBs in the developmental phase of newborn rats. The plasma of rats aged 2 to 18 months was used to detect the variation trend of βCBs and with some neurotransmitters. The plasma samples of normal C57BL/6 mice, APP/PS1 double transgenic mice, and scopolamine-induced memory impairment mice were collected and were analyzed to compare the difference of βCBs in different physiological states. The exposure levels of βCBs such as harmine, harmaline, and harmane in plasma of 550 healthy volunteers were also detected and analyzed on the basis of gender, race, and age.ResultsResults showed that harmine was the main compound found in rats, mice, and human, which can be detected in a newborn rat plasma (0.16 ± 0.03 ng/ml) and brain (0.33 ± 0.14 ng/g) without any exogenous consumption. The concentration of harmine in rat plasma showed a decreasing trend similar to the exposure levels of neurotransmitters such as 5-hydroxytryptamine, acetylcholine chloride, glutamic acid, tyrosine, and phenylalanine during the growth period of 18 months. The harmine exposure in rats and human indicates high dependence on the physiological and pathological status such as aging, gender, and race.ConclusionThe dynamic changes of harmine exposure in different animals and human, in vivo, at developmental and physiological states indicate that harmine is a naturally and widely distributed endogenous substance in different mammals and human. In addition to exogenous ingestion, spontaneous synthesis might be another important source of harmine in mammals, which should be verified by further experiment.

A Tara Gum/Olive Mill Wastewaters Phytochemicals Conjugate as a New Ingredient for the Formulation of an Antioxidant-Enriched Pudding

Olive mill wastewater, a high polyphenols agro-food by-product, was successfully exploited in an eco-friendly radical process to synthesize an antioxidant macromolecule, usefully engaged as a functional ingredient to prepare functional puddings. The chemical composition of lyophilized olive mill wastewaters (LOMW) was investigated by HPLC-MS/MS and 1H-NMR analyses, while antioxidant profile was in vitro evaluated by colorimetric assays. Oleuropein aglycone (5.8 μg mL−1) appeared as the main compound, although relevant amounts of an isomer of the 3-hydroxytyrosol glucoside (4.3 μg mL−1) and quinic acid (4.1 μg mL−1) were also detected. LOMW was able to greatly inhibit ABTS radical (IC50 equal to 0.019 mg mL−1), displaying, in the aqueous medium, an increase in its scavenger properties by almost one order of magnitude compared to the organic one. LOMW reactive species and tara gum chains were involved in an eco-friendly grafting reaction to synthesize a polymeric conjugate that was characterized by spectroscopic, calorimetric and toxicity studies. In vitro acute oral toxicity was tested against 3T3 fibroblasts and Caco-2 cells, confirming that the polymers do not have any effect on cell viability at the dietary use concentrations. Antioxidant properties of the polymeric conjugate were also evaluated, suggesting its employment as a thickening agent, in the preparation of pear puree-based pudding. High performance of consistency and relevant antioxidants features over time (28 days) were detected in the milk-based foodstuff, in comparison with its non-functional counterparts, confirming LOWM as an attractive source to achieve high performing functional foods.

An Updated Review on the Modulation of Carbon Partitioning and Allocation in Arbuscular Mycorrhizal Plants

Arbuscular mycorrhizal fungi (AMF) are obligate biotrophs that supply mineral nutrients to the host plant in exchange for carbon derived from photosynthesis. Sucrose is the end-product of photosynthesis and the main compound used by plants to translocate photosynthates to non-photosynthetic tissues. AMF alter carbon distribution in plants by modifying the expression and activity of key enzymes of sucrose biosynthesis, transport, and/or catabolism. Since sucrose is essential for the maintenance of all metabolic and physiological processes, the modifications addressed by AMF can significantly affect plant development and stress responses. AMF also modulate plant lipid biosynthesis to acquire storage reserves, generate biomass, and fulfill its life cycle. In this review we address the most relevant aspects of the influence of AMF on sucrose and lipid metabolism in plants, including its effects on sucrose biosynthesis both in photosynthetic and heterotrophic tissues, and the influence of sucrose on lipid biosynthesis in the context of the symbiosis. We present a hypothetical model of carbon partitioning between plants and AMF in which the coordinated action of sucrose biosynthesis, transport, and catabolism plays a role in the generation of hexose gradients to supply carbon to AMF, and to control the amount of carbon assigned to the fungus.

In Vitro and In Silico Kinetic Studies of Patented 1,7-diEthyl and 1,7-diMethyl Aminoalkanol Derivatives as New Inhibitors of Acetylcholinesterase

Two aminoalkanol derivatives of 1,7-diEthyl-8,9-diphenyl-4azatricyclo (5.2.1.02,6) dec-8-ene-3,5,10-trione and two derivatives of 1,7-diMethyl-8,9-diphenyl-4-azatricyclo (5.2.1.02.6) dec-8-ene-3,5,10-trione were evaluated in vitro for their inhibition efficacy of acetylcholinesterase. The Km, Vmax, slope angles of Lineweaver–Burk plots, Ki and IC50 values showed that all four aminoalkanol derivatives are competitive inhibitors of acetylcholinesterase whose inhibitory potency depends, to a varying extent, on the nature of the four different substituents present in the main compound structure. Studies have shown that the most potent acetylcholinesterase inhibitors are derivatives containing isopropylamine and/or methyl substituents in their structure. In contrast, dimethylamine and/or ethyl substituents seem to have a weaker, albeit visible, effect on the inhibitory potency of acetylcholinesterase. Additionally, docking studies suggest that studied compounds binds with the peripheral anionic site and not enter into the catalytic pocket due to the presence of the sterically extended substituent.

Anti-Dislipidemia Effectiveness Test of Turmeric Ethanol Extract (Curcuma Longa) in Male Wistar Mice Given a High-Fat Diet

Dyslipidemia is a condition of increasing levels of Low Density Lipoprotein (LDL), cholesterol in the blood, or triglycerides in the blood that can be accompanied by a decrease in levels of High Density Lipoprotein (HDL). Herbal products have been used since long ago in the medical world, one of which is curcuma longa root. The main compound of turmeric is curcumin which can lower cholesterol levels due to inhibiting cholesterol reabsorbtion from the outside and increase the enzyme HmgCoA reductase inhibitor so that fat synthesis can run properly. The purpose of this study was to find out the effectiveness of turmeric ethanol extract (Curcuma Longa) as an anti-dyslipidemia in male wistar rats given a high-fat diet. This experimental study with the pre-test and post-test group only control design approach was conducted in January 2021, at the Herbarium Medanese FMIPA USU. The size of the sample was calculated by Federer's formula, with at least 4 mice in each treatment group. The results and conclusions of turmeric ethanol (Curcuma Longa) III (150.20 ± 0.90 mg/dl) significantly decreased total cholesterol compared to the control group (177.50 ± 6.02mg/dl) (P value < 0.05). Turmeric ethanol extract (Curcuma Longa) III (110.00 (109-112) mg/dl) may significantly lower triglyceride levels compared to the control group (166.50 (160-175) mg/dl), (value P = 0.024). Turmeric ethanol extract (Curcuma Longa) III (66.50 ± 1.25 mg/dl) significantly lowered LDL levels compared to the control group (106.20 ± 3.50 mg/dl), (P value < 0.05). Turmeric ethanol extract (Curcuma Longa) III, (60.00 (59-61) mg/dl) can significantly increase HDL levels compared to the control group (27.00 (33-39) mg/dl), (Value P = 0.024). Turmeric ethanol extract (Curcuma Longa) III significantly lowered SGOT (Value = 0.024) and SGPT (Value P < 0.05) compared to the control group.

Effects of Curcuma Longa Ethanol Extract on Isolated Guinea Pigthile Smooth Muscle in Acetylcholine Induction

Epidemiological studies show that nearly 20% of the world's population suffers from diseases related to allergies and asthma. The main compound of turmeric is curcumin has several pharmacological properties, antioxidant properties, anti-inflammatory, asthma treatment. The study aimed to determine the effects of ethanol extract Curcuma longa on the smooth muscle of the isolated guinea pigtic trachea in acetylcholine induction. This research method was experimental to observe the relationship of Curcuma longa ethanol extract (EECL) to the relaxing effects of isolated smooth muscle trachea marmot (tracheal ring chain) inserted into a bath organ filled with Kreb's physiological fluid by maintaining a temperature of 35-370C and associated with a Matlab recorder. Samples used by male guinea pigs and ethanol extract Curcuma longa (EECL). The results of the study that ethanol extract Curcuma longa has a relaxing effect on the smooth muscles of the trachea isolated from the experimental rats contracted with acetylcholine. Ethanol extract Curcuma longa has the ability not dising from theophylline 2 x 10-4 M in reducing smooth muscle contraction of insulated Cavia porcelain trachea induced by acetylcholine, acetylcholine strength without incubation contraction compared to acetylcholine with EECL incubation showed statistically different results (p <0.05). The mechanism of Curcuma longa relaxation effect on isolated guinea pig smooth muscle is mediated through inhibition of the enzyme PDE.

Phyto-Phospholipid Conjugated Scorpion Venom Nanovesicles as Promising Carrier That Improves Efficacy of Thymoquinone against Adenocarcinoma Human Alveolar Basal Epithelial Cells

Lung cancer is a dangerous type of cancer in men and the third leading cause of cancer-related death in women, behind breast and colorectal cancers. Thymoquinone (THQ), a main compound in black seed essential oils, has a variety of beneficial effects, including antiproliferative, anti-inflammatory, and antioxidant properties. On the other hand, scorpion venom peptides (SV) induce apoptosis in the cancer cells, making it a promising anticancer agent. THQ, SV, and Phospholipon® 90H (PL) were incorporated in a nano-based delivery platform to assess THQ’s cellular uptake and antiproliferative efficacy against a lung cancer cell line derived from human alveolar epithelial cells (A549). Several nanovesicles were prepared and optimized using factorial experimental design. The optimized phytosome formulation contained 79.0 mg of PL and 170.0 mg of SV, with vesicle size and zeta potential of 209.9 nm and 21.1 mV, respectively. The IC50 values revealed that A549 cells were significantly more sensitive to the THQ formula than the plain formula and THQ. Cell cycle analysis revealed that THQ formula treatment resulted in significant cell cycle arrest at the S phase, increasing cell population in this phase by 22.1%. Furthermore, the THQ formula greatly increased cell apoptosis (25.17%) when compared to the untreated control (1.76%), plain formula (11.96%), or THQ alone (13.18%). The results also indicated that treatment with THQ formula significantly increased caspase-3, Bax, Bcl-2, and p53 mRNA expression compared to plain formula and THQ. In terms of the inflammatory markers, THQ formula significantly reduced the activity of TNF-α and NF-κB in comparison with the plain formula and THQ only. Overall, the findings from the study proved that a phytosome formulation of THQ could be a promising therapeutic approach for the treatment of lung adenocarcinoma.

Self-Healing Products of Cement Pastes with Supplementary Cementitious Materials, Calcium Sulfoaluminate and Crystalline Admixtures

The phase composition of self-healing products generated in cracks affects self-healing performance. This study investigated the self-healing products of cementitious materials using supplementary cementitious materials (SCMs), a calcium sulfoaluminate (CSA) expansion agent, and crystalline additives (CAs). Ground-granulated blast-furnace slag (GGBFS), fly ash (FA), and silica fume (SF) were used as SCMs, and anhydrite, Na2SO4, Na2CO3, and MgCO3 were used as crystalline additives (CAs). An artificial crack method was used to collect the self-healing products in the crack of the paste. The phase composition of the self-healing products was analyzed through X-ray diffraction (XRD)/Rietveld refinements and thermogravimetry/differential thermogravimetry (TG/DTG) analysis, and their morphology and ion concentration were examined through scanning electron microscopy with energy dispersive spectroscopy (SEM–EDS). From the results, the main compound of self-healing products was found to be calcite. GGBFS and FA decreased the content of portlandite, and the use of CAs led to the formation of alkali sulfate and alkali carbonate. The SEM–EDS analysis results showed that when GGBFS and FA were used, a large proportion of the self-healing products contained C-S-H and C-A-H, and the use of CSA led to the formation of monosulfate and ettringite.

Cabe Jawa (Piper retrofractum Vahl.) : PENGGUNAAN TRADISIONAL, FITOKIMIA dan AKTIVITAS FARMAKOLOGI Piper retrofractum Vahl. : Traditional Uses, Phytochemical and Pharmacological Activities

<em><em><em> </em></em></em><p align="center">ABSTRAK</p><p align="center"><strong> </strong></p><p>Cabe jawa<strong><em> (</em></strong><em>Piper</em><em> retrofractum</em> Vahl.) adalah tanaman daerah tropis asli Indonesia yang dijumpai juga di negara Asia Tenggara seperti Thailand dan Malaysia, dan sejak dahulu telah digunakan secara turun-temurun sebagai bahan tambahan makanan ataupun obat tradisional. Secara tradisional di masyarakat, buah cabe jawa<strong><em> </em></strong>dapat digunakan dalam ramuan untuk mengobati demam, perut kembung, mulas, muntah, mengatasi gangguan pencernaan, merangsang nafsu makan, dan lemah syahwat. Akarnya sering digunakan untuk mengobati sakit gigi, luka dan kejang, serta bagian daunnya digunakan juga untuk obat kumur. Beberapa penelitian menyebutkan aktivitas farmakologi cabe Jawa<strong><em> </em></strong>memiliki efek afrodisiaka, antipiretik, antihiperurisemia, antikanker, dan antimikroba. Pengujian klinis terhadap cabe jawa telah dilakukan dan potensial dikembangkan menjadi obat tradisional golongan fitofarmaka. Cabe jawa<strong><em> </em></strong>memiliki aktivitas sebagai imunostimulan, lebih tinggi dibandingkan dengan kelompok imunostimulan fitofarmaka. Cabe jawa<strong><em> </em></strong>mempunyai potensi sebagai anti-<em>photoaging</em>, aktivitas antituberkular, antiproliferasi, aktivitas larvasida, dan aktivitas sitotoksik. Studi fitokimia senyawa metabolit sekunder utama yang terkandung dalam cabe jawa<strong><em> </em></strong>antara lain beberapa jenis alkaloid seperti <em>piperine</em>, <em>pipernonaline</em>, <em>guineensine</em>, <em>piperoctadecalidine,</em> minyak atsiri buah cabe jawa mengandung tiga komponen utama yaitu yaitu <em>β</em>-<em>caryophyllene</em> (17%), <em>pentadecane</em> (17,8%) dan <em>β</em>- <em>bisabollene</em> (11,2%) . Selain senyawa utama tersebut, terdapat senyawa baru pada buah cabe jawa, diantaranya; senyawa amida, amida glikosida, fenilpropanoid glikosida, dan alkaloid. Sebagai afrodisiaka bagian yang digunakan adalah buahnya dan senyawa piperin yang diduga bertanggung jawab terhadap aktivitas tersebut. Piperin merupakan senyawa utama dan zat berkhasiat yang terkandung dalam buah<em> </em>cabe jawa dan berfungsi sebagai penurun demam, mengurangi rasa sakit, antioksidan, mengurangi peradangan, antitumor, dan sebagai imunomodulator. Berdasarkan aktifitas farmakologi yang baik dari cabe jawa maka studi atau penelitian-penelitian pada tanaman ini harus terus dilakukan seperti pengembangan formulasi dan upaya perbanyakan tanaman karena populasi cabe jawa jumlahnya terbatas. Media terbaik dalam induksi kalus tanaman cabe jawa adalah <em>Murrashige Skoog</em> (MS) yang ditambah 6-<em>Benzil Amino Purin</em> (BAP) dan <em>Naphtalene</em> <em>Acetic</em> <em>Acid</em> (NAA).</p><p align="center">ABSTRACT</p><p align="center"><strong><em> </em></strong></p><p><em>Piper retrofractum</em> vahl. is a tropical plant native to Indonesia which is also found in Southeast Asian countries such as Thailand and Malaysia, and has been used for generations as a food additive or traditional medicine. Traditionally in the community, <em>P. retrofractum </em> fruit can be used in potions to treat fever, flatulence, heartburn, vomiting, overcome digestive disorders, stimulate appetite, and impotence. The roots are often used to treat toothaches, wounds, and seizures, and the leaves are also used for mouthwash. Several studies have stated that the pharmacological activity of <em>P. retrofractum </em> has aphrodisiac, antipyretic, anticancer, and antimicrobial effects. Clinical testing on <em>P. retrofractum </em> has been carried out and has the potential to be developed into a traditional medicine of the phytopharmaceutical class. <em>P. retrofractum </em> has activity as an immunostimulant, which is higher than the phytopharmaceutical immunostimulant group. <em>P. retrofractum </em>has potential as anti-photoaging, antitubercular, antiproliferative, larvicidal activity, and cytotoxic activity. Phytochemical studies of the main secondary metabolites contained in P. rectofractum include several types of alkaloids such as piperine, pipernonaline, guineensine, piperoctadecalidine, fruit essential oils. Javanese chili contains three main components, namely-caryophyllene (17%), pentadecane (17.8%) and -bisabollene (11.2%). In addition to these main compounds, there are new compounds in <em>P. retrofractum </em> fruit, including; amide compounds, amide glucosides, phenylpropanoid glucosides, and alkaloids. As an aphrodisiac, the part used is the fruit and the piperine compound which is thought to be responsible for this activity. Piperine is the main compound and efficacious substance contained in <em>P. retrofractum </em> fruit and functions as a fever reducer, pain reliever, antioxidant, reducing inflammation, antitumor, and immunomodulator. Based on the good pharmacological activity of <em>P. retrofractum </em>, studies or researches on this plant must continue to be carried out such as formulation development and plant propagation efforts because the population of <em>P. retrofractum </em> is limited. The best medium for callus induction of cabe jawa was Murashige Skoog (MS) with 6-Benzyl Amino Purine (BAP) and Naphtalene acetic (NAA) added.</p><p> </p>

GC-MS analysis of young and mature wild agarwood leaves (Aquilaria malaccensis Lamk) and its antioxidant potential

Agarwood grows wildly in the nature and its leaves may be utilized as raw materials for agarwood tea, especially from Aquilaria species. The study was conducted to determine the chemical compounds in the young and mature leaves of wild gaharu (Aquilaria malaccensis Lamk). Chemical compounds were detected using pyrolysis gas chromatography mass spectrometry (py-GCMS) while antioxidant capacity of the leaf extracts was assayed using 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) free radical method. The results obtained a total of 30 chemical compounds in agarwood leaves extract with different composition between young and mature leaves. The agarwood leaves extracts displayed strong antioxidative capacity with a main compound namely octadecanoid acid or stearic acid.