The Effect of Melatonin Supplement on High Arterial Blood Pressure: An Overview from Clinicaltrials.gov.

Background: Melatonin is a hormone produced by the pineal gland primarily at night. It has been suggested that melatonin may possess various cardiovascular benefits, including the potential to lower blood pressure. For this reason, we sought to identify and provide evidence of the effectiveness of melatonin on high arterial blood pressure in clinical trials. Methods: Using the search term "melatonin and hypertension", a search of the ClinicalTrials.gov database was performed on October 10th, 2023. I defined the exclusion and inclusion criteria to isolate appropriate clinical trials. Inclusion criteria for the search included hypertension that utilized melatonin as a treatment supplement; all non-related trials were omitted from the search. The data extractions, including study title, study type, study status, and intervention and outcome details, were compiled. Results: Of the 13 clinical trials identified, only three focused on examining the effects of melatonin. The study titles, enrollment numbers, conditions, statuses, interventions, and outcome measures have been explained in depth. Information gathered from these clinical trials will assist us in identifying the possible risks and benefits of melatonin with respect to high arterial blood pressure. Conclusion: Melatonin has been shown to be an effective treatment for lowering blood pressure. More research is required to fully establish the potential benefits and risks and highlight the mechanisms through which melatonin may influence blood pressure regulation.

Computational Insights into Natural Antischistosomal Metabolites as SmHDAC8 Inhibitors: Molecular Docking, ADMET Profiling, and Molecular Dynamics Simulation.

Schistosomiasis is a neglected tropical disease with a significant socioeconomic impact. It is caused by several species of blood trematodes from the genus Schistosoma, with S. mansoni being the most prevalent. Praziquantel (PZQ) is the only drug available for treatment, but it is vulnerable to drug resistance and ineffective in the juvenile stage. Therefore, identifying new treatments is crucial. SmHDAC8 is a promising therapeutic target, and a new allosteric site was discovered, providing the opportunity for the identification of a new class of inhibitors. In this study, molecular docking was used to screen 13,257 phytochemicals from 80 Saudi medicinal plants for inhibitory activity on the SmHDAC8 allosteric site. Nine compounds with better docking scores than the reference were identified, and four of them (LTS0233470, LTS0020703, LTS0033093, and LTS0028823) exhibited promising results in ADMET analysis and molecular dynamics simulation. These compounds should be further explored experimentally as potential allosteric inhibitors of SmHDAC8.

Is music intervention effective in reducing anxiety and pain during breast biopsy procedure? A systematic review and meta-analysis of randomized controlled trials.

PURPOSE: To evaluate the evidence from randomized clinical trials (RCTs) about the effect of music intervention in reducing patients' anxiety during breast biopsy. METHODS: Electronic databases including PubMed, Cochrane Library, Scopus, and Web of Science were searched using the relevant MeSH terms. The inclusion criteria were all RCTs assessing the effect of music therapy versus no music in reducing anxiety during breast biopsy. The extracted outcomes were anxiety and pain during breast biopsy. They were pooled as mean difference (MD) with a 95% confidence interval (CI) in a fixed-effects model, using Review Manager 5.3 software for windows. The quality of included studies was assessed with the Cochrane risk of bias assessment tool (RoB 1.0). Then, the outcomes of our meta-analyses were independently evaluated by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) to know the grade of their evidence. RESULTS: The final analysis included five RCTs. We found a positive effect of music therapy in reducing anxiety levels compared with control group (MD = - 2.11; 95% CI (- 4.16 to - 0.06); p = 0.04). No difference between music and control groups regarding pain associated with breast biopsy (MD = 0.22; 95% CI (- 0.81 to 1.25); p = 0.68). The GRADE rating of our outcomes was low for anxiety levels and very low for pain during the biopsy. CONCLUSIONS: Music therapy could be an effective, simple, non-pharmacological option in relieving anxiety during breast biopsy; however, it had no effect on procedure-associated pain. More large and high-quality studies are needed to confirm our results.

Melanin Synthesis Inhibition Activity of Compounds Isolated from Bamboo Shoot Skin (Phyllostachys pubescens).

This study targets the evaluation of melanin synthesis inhibition activity of the bamboo shoot skin as agro-waste. The total methanolic extract of bamboo peel extract was evaluated for its skin protective effects via measuring its melanin inhibitory activity and its suppression activity on the expression of tyrosinase mRNA levels. Results showed that bamboo peel extract has a good ability for the inhibition of melanin synthesis so further studies were performed for the isolation of its constituents. Twelve compounds have been isolated from the shoot skin of Phyllostachys pubescens. Their structures were elucidated based on extensive spectroscopic methods. The melanin inhibition potential of the isolates was tested with their collagen-production-promoting activity for the determination of active principles. Results showed that Betulinic acid, tachioside, and 1,2-dilinolenin significantly suppressed melanin production per cell compared to control. Triacontanol, tricin, and (+)-lyoniresinol 9'-O-glucoside also tended to decrease melanin production per cell. These findings indicated that the skin of bamboo shoots, a significant agricultural waste, is a useful natural source for further research on its potential for aging problems such hyperpigmentation and cognitive function impairment.

Calendulaglycoside A showing potential activity against SARS-CoV-2 main protease: Molecular docking, molecular dynamics, and SAR studies.

BACKGROUND AND AIM: The discovery of drugs capable of inhibiting SARS-CoV-2 is a priority for human beings due to the severity of the global health pandemic caused by COVID-19. To this end, natural products can provide therapeutic alternatives that could be employed as an effective safe treatment for COVID-19. EXPERIMENTAL PROCEDURE: Twelve compounds were isolated from the aerial parts of C. officinalis L. and investigated for their inhibitory activities against SARS-CoV-2 Mpro compared to its co-crystallized N3 inhibitor using molecular docking studies. Furthermore, a 100 ns MD simulation was performed for the most active two promising compounds, Calendulaglycoside A (SAP5) and Osteosaponin-I (SAP8). RESULTS AND CONCLUSION: At first, molecular docking studies showed interesting binding scores as compared to the N3 inhibitor. Calendulaglycoside A (SAP5) achieved a superior binding than the co-crystallized inhibitor indicating promising affinity and intrinsic activity towards the Mpro of SARS-CoV-2 as well. Moreover, findings illustrated preferential stability for SAP5 within the Mpro pocket over that of N3 beyond the 40 ns MD simulation course. Structural preferentiality for triterpene-Mpro binding highlights the significant role of 17ß-glucosyl and carboxylic 3α-galactosyl I moieties through high electrostatic interactions across the MD simulation trajectories. Furthermore, this study clarified a promising SAR responsible for the antiviral activity against the SARS-CoV-2 Mpro and the design of new drug candidates targeting it as well. The above findings could be promising for fast examining the previously isolated triterpenes both pre-clinically and clinically for the treatment of COVID-19.

In silico study of natural compounds from sesame against COVID-19 by targeting Mpro, PLpro and RdRp.

Natural products and traditional medicine products with known safety profiles are a promising source for the discovery of new drug leads. Natural products as sesame were reported to exhibit potential to protect from COVID-19 disease. In our study, the total methanolic extract of Sesamum indicum L. seeds (sesame) were led to isolation of seven known compounds, five lignan; sesamin 1, sesamolin 2, pinoresinol 3, hydroxymatairesinol 6, spicatolignan 7, together with two simple phenolic compounds; ferulic acid 4 and vanillic acid 5. All isolated compounds were evaluated in silico against three important SARS-CoV-2 protein targets; main protease (Mpro), papain-like protease (PLpro) and RNA-dependent RNA polymerase (RdRp) which possessed crucial role in replication and proliferation of the virus inside the human cell. The results revealed that compound 6 has the high affinity against the three main proteins, specially towards the SARS-CoV-2 Mpro that exceeded the currently used SARS-CoV-2 Mpro inhibitor darunavir as well as, exhibiting a similar binding energy at SARS CoV-2 PLpro when compared with the co-crystallized ligand. This activity continued to include the RdRp as it displayed a comparable docking score with remdesivir. Inferiorly, compounds 1 and 2 showed also similar triple inhibitory effect against the three main proteins while compound 7 exhibited a dual inhibitory effect against SARS CoV-2 PLPro and RdRp. Further molecular dynamic simulation experiments were performed to validate these docking experiments and to calculate their binding free energies (ΔGs). Compounds 1, 2, 3, 6, and 7 showed comparable binding stability inside the active site of each enzyme with ΔG values ranged from -4.9 to -8.8 kcal mol-1. All the compounds were investigated for their ADME and drug likeness properties, which showed acceptable ADME properties and obeying Lipinski's rule of five parameters. It can be concluded that the isolated compounds from sesame lignans could be an alternative source for the development of new natural leads against COVID-19.

New sesquiterpene glycoside ester with antiprotozoal activity from the flowers of Calendula officinalis L.

Continued chromatographic investigation of Calendula officinalis flowers led to the isolation of two sesquiterpenes, including one new, viridiflorol-10-O-ß-quinovopyranoside-2`-O-(3``-methyl-2``-pentenoate) (1), along with a previously reported compound viridiflorol-10-O-ß-fucopyranoside-2`-O-(3``-methyl-2``-pentenoate) (2). The new compound 1 was tested for antiprotozoal activity against Leishmania donovani Amastigote/THP1 and Trypanosoma brucei and it showed IC50 values of 3.57 and 7.84 µg/mL, respectively, while compound 2 exhibited no activity at the highest concentration tested 10 µg/mL.

A new glucoside with a potent α-glucosidase inhibitory activity from Lycium schweinfurthii.

A new glucoside, 3-methoxy-4-O-ß-D-glucopyranosyl-methyl benzoate, has been isolated from Lycium schweinfurthii along with five known compounds through bioactivity guided fractionation of the total plant methanolic extract towards α-glucosidase inhibitory activity. All the isolated compounds were tested for their inhibitory effect on α-glucosidase enzyme. As a result, four of them showed a potent inhibitory activity and thus constitute a therapeutic approach to decrease postprandial hyperglycemia in diabetic patients.

A new aliphatic ester of hydroxysalicylic acid from fermented Carica papaya L. preparation with a potential hair growth stimulating activity.

An aliphatic ester of hydroxysalicylic acid (6), reported for the first time from a natural source in addition to five known compounds were isolated from the fermented Carica papaya L. preparation, a commercialized functional food. The known compounds were identified as 5-hydroxymethylfurfuraldehyde (1), trans-caffeic acid (2), butyl 4-hydroxybenzoate (butylparaben) (3), lycopene (4), benzyl isothiocyanate (5). Compounds 1 and 3 were reported for the first time from Papaya fruits through this study. The new compound showed a moderate antioxidant activity and a potent hair growth stimulating activity in vitro.

Rho-kinase inhibitors from adlay seeds.

Rho-kinase enzymes are one of the most important targets recently identified in our bodies. Several lines of evidence indicate that these enzymes are involved in many diseases and cellular disorders. ROCK inhibitors may have clinical applications for cancer, hypertension, glaucoma, etc. Our study aims to identify the possible involvement of Rho-kinase inhibition to the multiple biological activities of adlay seeds and provide a rationale for their folkloric medicines. Hence, we evaluated Rho-kinase I and II inhibitory activity of the ethanol extract and 28 compounds derived from the seeds. A molecular docking assay was designed to estimate the binding affinity of the tested compounds with the target enzymes. The results of our study suggest a possible involvement of Rho-kinase inhibition to the multiple biological activities of the seeds. Furthermore, the results obtained with the tested compounds revealed some interesting skeletons as a scaffold for design and development of natural Rho-kinase inhibitors.

Melanogenesis inhibitors from Coix lacryma-jobi seeds in B16-F10 melanoma cells.

An adenine derivative, 9-ß-D-glucopyranosyl adenine, reported for the first time from a natural source, in addition to nine known compounds were isolated from the seeds of Coix lacryma-jobi. Their structures were elucidated based on extensive spectroscopic and chemical studies. The isolated compounds and the ethanol extract have been assayed for melanin inhibition using B16-F10 melanoma cell line. The results of our study suggested the potential use of Coix lacryma-jobi seeds as a skin whitening agent and reveal the seeds to be a rich source of important phytochemicals with melanogenesis inhibitory activity. Among the isolated compounds, coixol (2) and 2-O-ß-glucopyranosyl-7-methoxy-2H-1,4-benzoxazin-3(4H)-one (8) exhibited potent melanogenesis inhibitory activity with no obvious melanocytotoxicity. The rest of the compounds showed weak to moderate activity.

Partial contribution of Rho-kinase inhibition to the bioactivity of Ganoderma lingzhi and its isolated compounds: insights on discovery of natural Rho-kinase inhibitors.

Recent studies identified Rho-kinase enzymes (ROCK-I and ROCK-II) as important targets that are involved in a variety of diseases. Synthetic Rho-kinase inhibitors have emerged as potential therapeutic agents to treat disorders such as hypertension, stroke, cancer, diabetes, glaucoma, etc. Our study is the first to screen the total ethanol extract of the medicinal mushroom Ganoderma lingzhi with thirty-five compounds for Rho-kinase inhibitory activity. Moreover, a molecular binding experiment was designed to investigate the binding affinity of the compounds at the active sites of Rho-kinase enzymes. The structure-activity relationship analysis was investigated. Our results suggest that the traditional uses of G. lingzhi might be in part due to the ROCK-I and ROCK-II inhibitory potential of this mushroom. Structure-activity relationship studies revealed some interesting features of the lanostane triterpenes that potentiate their Rho-kinase inhibition. These findings would be helpful for further studies on the design of Rho-kinase inhibitors from natural sources and open the door for contributions from other researchers for optimizing the development of natural Rho-kinase inhibitors.

Acetylcholine esterase inhibitors and melanin synthesis inhibitors from Salvia officinalis.

BACKGROUND: Salvia officinalis is a traditionally used herb with a wide range of medicinal applications. Many phytoconstituents have been isolated from S. officinalis, mainly phenolic diterpenes, which possess many biological activities. PURPOSE: This study aimed to evaluate the ability of the phenolic diterpenes of S. officinalis to inhibit acetylcholine esterase (AChE) as well as their ability to inhibit melanin biosynthesis in B16 melanoma cells. METHODS: The phenolic diterpenes isolated from the aerial parts of S. officinalis were tested for their effect on melanin biosynthesis in B16 melanoma cell lines. They were also tested for their ability to inhibit AChE using Ellman's method. Moreover, a molecular docking experiment was used to investigate the binding affinity of the isolated phenolic diterpenes to the amino acid residues at the active sites of AChE. RESULTS: Seven phenolic diterpenes-sageone, 12-methylcarnosol, carnosol, 7b-methoxyrosmanol, 7a-methoxyrosmanol, isorosmanol and epirosmanol-were isolated from the methanolic extract of the aerial parts of S. officinalis. Isorosmanol showed a melanin-inhibiting activity as potent as that of arbutin. Compounds 7a-methoxyrosmanol and isorosmanol inhibited AChE activity by 50% and 65%, respectively, at a concentration of 500 µM. CONCLUSIONS: The results suggest that isorosmanol is a promising natural compound for further studies on development of new medications which might be useful in ageing disorders such as the declining of cognitive functions and hyperpigmentation.

Lucidumol C, a new cytotoxic lanostanoid triterpene from Ganoderma lingzhi against human cancer cells.

A new oxygenated lanostane-type triterpene, named lucidumol C, together with six known compounds, was isolated from the chloroform extract of the fruiting bodies of Ganoderma lingzhi. Structures were established based on extensive spectroscopic and chemical studies. Potential cytotoxic activities of the isolated compounds were evaluated against human colorectal carcinoma (HCT-116, Caco-2), human liver carcinoma (HepG2), and human cervical carcinoma (HeLa) cell lines using WST-1 reagent. Selectivity was evaluated using normal human fibroblast cells (TIG-1 and HF19). Among the compounds, lucidumol C showed potent selective cytotoxicity against HCT-116 cells with an IC50 value of 7.86 ± 4.56 µM and selectivity index (SI) >10 with remarkable cytotoxic activities against Caco-2, HepG2 and HeLa cell lines.

Biological Activities of Oleanolic Acid Derivatives from Calendula officinalis Seeds.

Phytochemical examination of butanol fraction of Calendula officinalis seeds led to the isolation of two compounds identified as 28-O-ß-D-glucopyranosyl-oleanolic acid 3-O-ß-D-glucopyranosyl (1→3)-ß-D-glucopyranosiduronic acid (CS1) and oleanolic acid 3-O-ß-D-glucopyranosyl (1→3)-ß-D-glucopyranosiduronic acid (CS2). Biological evaluation was carried out for these two compounds such as melanin biosynthesis inhibitory, hyaluronic acid production activities, anti obesity using lipase inhibition and adipocyte differentiation as well as evaluation of the protective effect against hydrogen peroxide induced neurotoxicity in neuro-2A cells. The results showed that, compound CS2 has a melanin biosynthesis stimulatory activity; however, compound CS1 has a potent stimulatory effect for the production of hyaluronic acid on normal human dermal fibroblast from adult (NHDF-Ad). Both compounds did not show any inhibitory effect on both lipase and adipocyte differentiation. Compound CS2 could protect neuro-2A cells and increased cell viability against H2 O2 . These activities (melanin biosynthesis stimulatory and protective effect against H2 O2 of CS2 and hyaluronic acid productive activities of these triterpene derivatives) have been reported for the first time. Copyright © 2016 John Wiley & Sons, Ltd.

Biological Activities of Extracts from Different Parts of Cryptomeria japonica.

Cryptomeria japonica is one of the most important forest tree species in Japan. To increase the demand for domestic timber, broad uses related to the functional attributes of C. japonica must be developed. Several studies have examined the usefulness of C. japonica in terms of its biological activities, but a comprehensive study subjecting all parts of the C. japonica plant to the same solvent for extraction has not been done. Here, methanol extractions from the leaves, branches, bearing branches, male flowers, female flowers, cones, bark, heartwood, sapwood, pith, rhizomes, roots, and pollen were subjected to several in vitro assays of their biological activities such as antioxidant activity, anti-lipase activity, antibacterial activity and melanin-biosynthesis-inhibition activity. Their total phenolic content was also determined. The methanol extracts from each part of C. japonica except for pollen showed strong activities in the bioactivity assays. Furthermore, the methanol extracts were analyzed by GC/MS. The phytochemical profile varied among extracts from various parts of C. japonica. Our results suggest the great potential of C. japonica for use as a functional ingredient in health-related products.

A structure-activity relationship study on antiosteoclastogenesis effect of triterpenoids from the leaves of loquat (Eriobotrya japonica).

Our previous results elucidated that the leaves of Eriobotrya japonica possessed the potential to suppress ovariectomy-induced bone mineral density deterioration, and ursolic acid, the major bioactive component in these leaves, suppressed the osteoclast differentiation. The aim of this study was to discover more candidates for development of novel antiosteoclastogenesis agents from the leaves of E. japonica. Phytochemical analysis following a cell-based osteoclastic tartrate-resistant acid phosphatase (TRAP) activity assay revealed 11 more compounds with a potent antiosteoclastogenesis effect. The potency of ursane-type triterpenoids from the leaves of E. japonica prompted us to investigate the structure-activity relationships underlying their antiosteoclastogenesis. The results revealed that both the hydroxyl group at C-3 and the carboxylic group at C-17 played indispensable roles in the antiosteoclastogenesis activity of ursane-type triterpenoids. The configuration at C-3 (a beta-form of the hydroxyl group) was found to be important for this activity. While introducing a hydroxyl group at C-19 increased the inhibitory activity of ursane-type triterpenoids carrying an alpha-form hydroxyl group at C-3. The bioactivity analyses of ursolic acid and oleanolic acid demonstrated that the antiosteoclastogenesis effect of ursolic acid may be related to different positions of the C-29 and C-30 methyl groups on the E-ring, since oleanolic acid showed limited activity. The addition of a hydroxyl group at C-2 would dramatically improve the inhibition of oleanane-type triterpenoids. Collectively, these findings could provide important clues for the improvement of multi-targeted antiosteoclastogenesis agents from the leaves of E. japonica.

Multiple Biological Effects of Olive Oil By-products such as Leaves, Stems, Flowers, Olive Milled Waste, Fruit Pulp, and Seeds of the Olive Plant on Skin.

As olive oil production increases, so does the amount of olive oil by-products, which can cause environmental problems. Thus, new ways to utilize the by-products are needed. In the present study, five bioactive characteristics of olive oil by-products were assessed, namely their antioxidant, anti-bacterial, anti-melanogenesis, anti-allergic, and collagen-production-promoting activities. First, the extracts of leaves (May and October), stems (May and October), flowers, olive milled waste, fruit pulp and seeds were prepared using two safe solvents, ethanol and water. According to HPLC and LC/MS analysis and Folin-Ciocalteu assay, the ethanol extracts of the leaves (May and October), stems (May and October) and flowers contained oleuropein, and the ethanol extract of the stems showed the highest total phenol content. Oleuropein may contribute to the antioxidant and anti-melanogenesis activities of the leaves, stems, and flowers. However, other active compounds or synergistic effects present in the ethanol extracts are also likely to contribute to the anti-bacterial activity of the leaves and flowers, the anti-melanogenesis activity of some parts, the anti-allergic activity of olive milled waste, and the collagen-production-promoting activity of the leaves, stems, olive milled waste and fruit pulp. This study provides evidence that the by-products of olive oil have the potential to be further developed and used in the skin care industry.

Corncobs as a potential source of functional chemicals.

Phytochemical examination of corncob extracts led to the isolation of a new lignan identified as 7,7'-dihydroxy-3'-O-demethyl-4-methoxymatairesinol, together with seven known compounds, identified as ß-sitosterol, ß-sitosteryl-ß-D-glucoside, 6ß-hydroxy-campest-4-en-3-one, 5α,8α-epidioxyergosta-6,22-dien-3ß-ol, tricin, kaempferol and p-coumaric acid. The isolated compounds were identified by one and two-dimensional NMR spectroscopies and mass spectrometry.

An alkali-soluble heteroxylan from seeds of Phoenix dactylifera L.

Alkali-soluble polysaccharides, isolated from the seeds of dates, have been investigated using methylation and partial hydrolysis studies. The polysaccharides are shown to contain D-xylose and 4-O-methyl-D-glucuronic acid in a molar ratio of 5:1. An aldobiouronic acid from hemicellulose was characterized, and investigation revealed that the hemicellulose consists of a polymer of (1-->4)-linked D-xylopranosyl residues having branches of D-xylopyranosyl and 4-O-methyl-alpha-D-glucopyranosyluronic acid.