Radiosynthesis, Stability, Lipophilicity, and Cellular Uptake Evaluations of [131I]Iodine-α-Mangostin for Breast Cancer Diagnosis and Therapy.

The high rate of incidence and mortality caused by breast cancer encourage urgent research to immediately develop new diagnostic and therapeutic agents for breast cancer. Alpha mangostin (AM) is a natural compound reported to have anti-breast cancer properties. Its electron-donating groups structure allows it to be labeled with an iodine-131 radioisotope to develop a candidate of a diagnostic and therapeutic agent for breast cancer. This study aims to prepare the [131I]Iodine-α-mangostin ([131I]I-AM) and evaluate its stability, lipophilicity, and cellular uptake in breast cancer cell lines. The [131I]I-AM was prepared by direct radiosynthesis with Chloramine-T method in two conditions (A: AM dissolved in NaOH, B: AM dissolved in ethanol). Reaction time, pH, and mass of the oxidizing agent were optimized as crucial parameters that affected the radiosynthesis reaction. Further analysis was conducted using the radiosynthesis conditions with the highest radiochemical purity (RCP). Stability tests were carried out at three storage conditions, including -20, 2, and 25 °C. A cellular uptake study was performed in T47D (breast cancer cell line) and Vero cells (noncancerous cell line) at various incubation times. The results show that the RCP values of [131I]I-AM under conditions A and B were 90.63 ± 0.44 and 95.17 ± 0.80% (n = 3), respectively. In the stability test, [131I]I-AM has an RCP above 90% after three days of storage at -20 °C. A significant difference was obtained between [131I]I-AM uptake in T47D and Vero cells. Based on these results, [131I]I-AM has been prepared with high RCP, stable at -20 °C, and specifically uptaken by breast cancer cell lines. Biodistribution evaluations in animals are recommended as further research in developing [131I]I-AM as a diagnostic and therapeutic agent for breast cancer.

Analysis of Essential Oils Components from Aromatic Plants Using Headspace Repellent Method against Aedes aegypti Mosquitoes.

This research serves as the basis for developing essential oil-based repellent activity tests against Aedes aegypti mosquitoes. The method used for the isolation of essential oils was the steam distillation method. Virus-free Aedes aegypti mosquitoes were used as test animals by applying the 10% essential oil repellent on the arms of volunteers. The analysis of the essential oils activities and aromas' components was carried out using headspace repellent and GC-MS methods. Based on the results, the yields of essential oil from 5000 g samples for cinnamon bark, clove flowers, patchouli, nutmeg seed, lemongrass, citronella grass, and turmeric rhizome were 1.9%, 16%, 2.2%, 16.8%, 0.9%, 1.4%, and 6.8%, respectively. The activity test showed that the average repellent power of 10% essential oils, patchouli, cinnamon, nutmeg, turmeric, clove flowers, citronella grass, and lemongrass, was 95.2%, 83.8%, 71.4%, 94.7%, 71.4%, 80.4%, and 85%, respectively. Patchouli and cinnamon had the best average repellent power. Meanwhile, the aroma activities showed that the average repellent power of the patchouli oil was 96%, and the cinnamon oil was 94%. From the GC-MS analysis, nine components were identified in the patchouli essential oil aromas' with the highest concentration being patchouli alcohol (42.7%), Azulene, 1,2,3,5,6,7,8,8a-octahydro-1,4-dimethyl-7-(1-methylethenyl)-, [1S-(1α,7α,8aß)] (10.8%), α-guaiene (9.22%), and seychellene (8.19%)., whereas using the GC-MS headspace repellent method showed that there were seven components identified in the patchouli essential oil aroma with a high concentration of the components, which were patchouli alcohol (52.5%), Seychellene (5.2%), and α-guaiene (5.2%). The analysis results of cinnamon essential oil using the GC-MS method showed that there were five components identified in the aroma, with E-cinnamaldehyde (73%) being the highest component, whereas using the GC-MS headspace repellent method showed that there were five components identified in the aroma, with highest concentrations of cinnamaldehyde (86.1%). It can be concluded that the chemical compounds contained in patchouli and cinnamon bark have the potential to be environmentally friendly repellents in controlling and preventing Aedes aegypti mosquitoes.

The Effects of Antioxidants from Natural Products on Obesity, Dyslipidemia, Diabetes and Their Molecular Signaling Mechanism.

Obesity is a risk factor that leads to the development of other diseases such as dyslipidemia and diabetes. These three metabolic disorders can occur simultaneously, hence, the treatment requires many drugs. Antioxidant compounds have been reported to have activities against obesity, dyslipidemia and diabetes via several mechanisms. This review aims to discuss the antioxidant compounds that have activity against obesity, dyslipidemia and diabetes together with their molecular signaling mechanism. The literature discussed in this review was obtained from the PUBMED database. Based on the collection of literature obtained, antioxidant compounds having activity against the three disorders (obesity, dyslipidemia and diabetes) were identified. The activity is supported by various molecular signaling pathways that are influenced by these antioxidant compounds, further study of which would be useful in predicting drug targets for a more optimal effect. This review provides insights on utilizing one of these antioxidant compounds as opposed to several drugs. It is hoped that in the future, the number of drugs in treating obesity, dyslipidemia and diabetes altogether can be minimized consequently reducing the risk of side effects.

Signaling Pathways and Natural Compounds in Triple-Negative Breast Cancer Cell Line.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, having a poor prognosis and rapid metastases. TNBC is characterized by the absence of estrogen, progesterone, and human epidermal growth receptor-2 (HER2) expressions and has a five-year survival rate. Compared to other breast cancer subtypes, TNBC patients only respond to conventional chemotherapies, and even then, with limited success. Shortages of chemotherapeutic medication can lead to resistance, pressured index therapy, non-selectivity, and severe adverse effects. Finding targeted treatments for TNBC is difficult owing to the various features of cancer. Hence, identifying the most effective molecular targets in TNBC pathogenesis is essential for predicting response to targeted therapies and preventing TNBC cell metastases. Nowadays, natural compounds have gained attention as TNBC treatments, and have offered new strategies for solving drug resistance. Here, we report a systematic review using the database from Pubmed, Science Direct, MDPI, BioScince, Springer, and Nature for articles screening from 2003 to 2022. This review analyzes relevant signaling pathways and the prospect of utilizing natural compounds as a therapeutic agent to improve TNBC treatments in the future.

Decaffeination and Neuraminidase Inhibitory Activity of Arabica Green Coffee (Coffea arabica) Beans: Chlorogenic Acid as a Potential Bioactive Compound.

Coffee has been studied for its health benefits, including prevention of several chronic diseases, such as type 2 diabetes mellitus, cancer, Parkinson's, and liver diseases. Chlorogenic acid (CGA), an important component in coffee beans, was shown to possess antiviral activity against viruses. However, the presence of caffeine in coffee beans may also cause insomnia and stomach irritation, and increase heart rate and respiration rate. These unwanted effects may be reduced by decaffeination of green bean Arabica coffee (GBAC) by treatment with dichloromethane, followed by solid-phase extraction using methanol. In this study, the caffeine and chlorogenic acid (CGA) level in the coffee bean from three different areas in West Java, before and after decaffeination, was determined and validated using HPLC. The results showed that the levels of caffeine were reduced significantly, with an order as follows: Tasikmalaya (2.28% to 0.097% (97 ppm), Pangalengan (1.57% to 0.049% (495 ppm), and Garut (1.45% to 0.00002% (0.2 ppm). The CGA levels in the GBAC were also reduced as follows: Tasikmalaya (0.54% to 0.001% (118 ppm), Pangalengan (0.97% to 0.0047% (388 ppm)), and Garut (0.81% to 0.029% (282 ppm). The decaffeinated samples were then subjected to the H5N1 neuraminidase (NA) binding assay to determine its bioactivity as an anti-influenza agent. The results show that samples from Tasikmalaya, Pangalengan, and Garut possess NA inhibitory activity with IC50 of 69.70, 75.23, and 55.74 µg/mL, respectively. The low level of caffeine with a higher level of CGA correlates with their higher levels of NA inhibitory, as shown in the Garut samples. Therefore, the level of caffeine and CGA influenced the level of NA inhibitory activity. This is supported by the validation of CGA-NA binding interaction via molecular docking and pharmacophore modeling; hence, CGA could potentially serve as a bioactive compound for neuraminidase activity in GBAC.

Natural Flavonoids as Potential Angiotensin-Converting Enzyme 2 Inhibitors for Anti-SARS-CoV-2.

Over the years, coronaviruses (CoV) have posed a severe public health threat, causing an increase in mortality and morbidity rates throughout the world. The recent outbreak of a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the current Coronavirus Disease 2019 (COVID-19) pandemic that affected more than 215 countries with over 23 million cases and 800,000 deaths as of today. The situation is critical, especially with the absence of specific medicines or vaccines; hence, efforts toward the development of anti-COVID-19 medicines are being intensively undertaken. One of the potential therapeutic targets of anti-COVID-19 drugs is the angiotensin-converting enzyme 2 (ACE2). ACE2 was identified as a key functional receptor for CoV associated with COVID-19. ACE2, which is located on the surface of the host cells, binds effectively to the spike protein of CoV, thus enabling the virus to infect the epithelial cells of the host. Previous studies showed that certain flavonoids exhibit angiotensin-converting enzyme inhibition activity, which plays a crucial role in the regulation of arterial blood pressure. Thus, it is being postulated that these flavonoids might also interact with ACE2. This postulation might be of interest because these compounds also show antiviral activity in vitro. This article summarizes the natural flavonoids with potential efficacy against COVID-19 through ACE2 receptor inhibition.

General toxicity studies of alpha mangostin from Garcinia mangostana: A systematic review.

Alpha mangostin (AM), the main xanthone derivative contained in mangosteen pericarp (Garcinia mangostana/GM), has many pharmacological activities such as antioxidant, antiproliferation, antiinflammatory, and anticancer. Several general toxicity studies of AM have been previously reported to assess the safety profile of AM. Toxicity studies were carried out by various methods such as on test animals, interventions, and various routes of administration, but the test results have not been well documented. Our study aimed to systematically summarizes research on the safety profile of GM containing AM through general toxicity tests to get the LD50 and NOAEL values, and so, can be used as a database related to AM toxicity profiles. This could facilitate other researchers in determining further development of GM-or-AM-based products. Pubmed, Google scholar, ScienceDirect, and EBSCO were chosen to collect the articles while ARRIVE 2.0 was used to evaluate the quality and risk-of-bias of the in vivo toxicity studies included in this systematic review. A total of 20 articles met the eligibility criteria and were reviewed to predict the LD50 and NOAEL of AM. The results showed that the LD50 of AM is between >15.480 mg/kgBW to ≤6000 mg/kgBW while the NOAEL value is between <100 and ≤2000 mg/kgBW.

Isolation of phenolic compound from Lawsonia inermis and its prediction as anti-diabetic agent using molecular docking and molecular dynamic simulation.

High blood sugar is a defining feature of chronic disease, diabetes mellitus (DM). There are numerous commercially available medications for the treatment of DM. However, managing the patient's glucose levels remain a challenge because of the gradual reduction in beta-cell function and some side effects from the long-term use of various medications. Previous research has shown that the phenolic compound of henna plant (Lawsonia inermis L.) has the potential as anti-diabetic agent since it is able to suppress the digesting of α-amylase enzyme. In these studies, the plant' phenolic compounds have been isolated and characterized using UV, IR, NMR and LC-MS methods. Furthermore, the compound interaction into the active site of the α-amylase enzyme has been analyzed using molecular docking and molecular dynamics, as well as into α-glucosidase enzyme for predicting of the affinities. The results showed that isolated compound has the molecular formula of C15H10O6 with eleven degrees of unsaturation (DBE; double bond equivalence). The DBE value corresponds to the structure of the luteolin compound having an aromatic ring (8), a carbonyl group on the side chain (1) and a ketone ring with (2). The interaction study of the isolated compound with α-amylase and α-glucosidase enzyme using molecular docking compared to the positive control (acarbose) gave binding energy of -8.03 and -8.95 kcal/mol, respectively. The molecular dynamics simulation using the MM-PBSA method, complex stability based on solvent accessible surface area (SASA), root mean square deviation (RMSD), and root mean square fluctuation (RMSF) revealed that the compound has a high affinity for receptors. The characteristics of skin permeability, absorption, and distribution using ADME-Tox model were also well predicted. The results indicate that the phenolic compound isolated from L. inermis leaf was luteolin and it has the potential as an anti-diabetic agent.Communicated by Ramaswamy H. Sarma.

Pulse Crop Genetics for a Sustainable Future: Where We Are Now and Where We Should Be Heading.

The last decade has witnessed dramatic changes in global food consumption patterns mainly because of population growth and economic development. Food substitutions for healthier eating, such as swapping regular servings of meat for protein-rich crops, is an emerging diet trend that may shape the future of food systems and the environment worldwide. To meet the erratic consumer demand in a rapidly changing world where resources become increasingly scarce due largely to anthropogenic activity, the need to develop crops that benefit both human health and the environment has become urgent. Legumes are often considered to be affordable plant-based sources of dietary proteins. Growing legumes provides significant benefits to cropping systems and the environment because of their natural ability to perform symbiotic nitrogen fixation, which enhances both soil fertility and water-use efficiency. In recent years, the focus in legume research has seen a transition from merely improving economically important species such as soybeans to increasingly turning attention to some promising underutilized species whose genetic resources hold the potential to address global challenges such as food security and climate change. Pulse crops have gained in popularity as an affordable source of food or feed; in fact, the United Nations designated 2016 as the International Year of Pulses, proclaiming their critical role in enhancing global food security. Given that many studies have been conducted on numerous underutilized pulse crops across the world, we provide a systematic review of the related literature to identify gaps and opportunities in pulse crop genetics research. We then discuss plausible strategies for developing and using pulse crops to strengthen food and nutrition security in the face of climate and anthropogenic changes.

Stable Production of the Antimalarial Drug Artemisinin in the Moss Physcomitrella patens.

Malaria is a real and constant danger to nearly half of the world's population of 7.4 billion people. In 2015, 212 million cases were reported along with 429,000 estimated deaths. The World Health Organization recommends artemisinin-based combinatorial therapies, and the artemisinin for this purpose is mainly isolated from the plant Artemisia annua. However, the plant supply of artemisinin is irregular, leading to fluctuation in prices. Here, we report the development of a simple, sustainable, and scalable production platform of artemisinin. The five genes involved in artemisinin biosynthesis were engineered into the moss Physcomitrella patens via direct in vivo assembly of multiple DNA fragments. In vivo biosynthesis of artemisinin was obtained without further modifications. A high initial production of 0.21 mg/g dry weight artemisinin was observed after only 3 days of cultivation. Our study shows that P. patens can be a sustainable and efficient production platform of artemisinin that without further modifications allow for industrial-scale production. A stable supply of artemisinin will lower the price of artemisinin-based treatments, hence become more affordable to the lower income communities most affected by malaria; an important step toward containment of this deadly disease threatening millions every year.