Current Bioactive Compounds - Volume 19, Issue 1, 2023

Aim: The aim of the present study is to examine the effect of estradiol on chondrocyte inflammatory potential and apoptosis in a mouse model of osteoarthritis (OA). Background: OA is a degenerative joint disease related to articular cartilage disintegration, together with substantial changes in the subchondral bone. Estradiol (ED) is considered to be an important player in maintaining bone homeostasis. Increasing evidence support the association between the severity of cartilage erosion and chondrocyte death. Objective: It is of great importance to elucidate the role of chondrocytes in the development of OA in relation to estrogen levels. Methods: The present work was conducted on a model of collagenase-induced osteoarthritis (CIOA) in ICR (CD-2) mice. The cytokine and MMP-3 concentrations were assayed by ELISA, and apoptosis of chondrocytes was determined by flow cytometry. Results: ED decreased the number of cultured TGF-β1 positive chondrocytes, reduced the percentage of double-positive CD220+/TNF-α+ chondrocytes. ED reduced the rate of apoptosis and MMP- 13 production of stimulated arthritic chondrocytes, and inhibited the release of inflammatory IL-6 and IL-8 cytokines in vitro. Conclusion: Our results show that ED affects chondrocyte functions as a part of its anti-arthritic mechanism of action and it might be a perspective drug for healing OA.

Background: The Pulicaria genus (Asteraceae family) plays a remarkable role in the development of drugs used in modern medicine. Leaf extracts of Pulicaria odora harvested in Bejaia were evaluated for their antioxidant and antimicrobial activities. Methods: HCl method at three different wavelengths (280, 320, and 360 nm) was carried out for total phenolic content and characterized by ultra-performance liquid chromatography (UPLC) analysis. Antimicrobial activity was evaluated using four bacterial strains (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Listeria innocua) and three molds (Aspergillus flavus, Aspergillus niger, and Trichoderma reesei). Four antioxidant tests (ORAC, ABTS, DPPH, and FRAP) were performed. Results: The extracts had high total polyphenols (305 mg catechin equivalents [CE]), flavonols (56 mg quercetin equivalents [QE]), tannins (77 mg CE) and tartaric acids (38 mg caffeic acid equivalents [CAE]) per g dry matter contents. UPLC analysis of the 70% ethanol extracts showed abundant phenolic acids (protocatechuic, chlorogenic, and caffeic acids). Pulicaria odora extracts exhibited good antimicrobial activity against bacterial (∼18 mm inhibition zones) and molds (11.3- 17.3 mm) strains. Conclusion: All extracts displayed good antioxidant activity and effective antimicrobial activity, enabling their use as a conservative agent or therapeutic remedy.

Background: Mostly, Moringa plants (Moringa oleifera Lam.) are commercially propagated by seeds; however, there are some plantations from stem cuttings. Thus, seedling populations show a high morphological diversity level due to segregation. In particular, differences in leaf color can be commonly observed. This work aimed to characterize leaf color from different moringa plants and relate it to phenolic leaf content, including some flavonoids, and to the DPPH radical scavenging activity of leaf extracts. Methods: Three plants with red leaf petioles and three plants with green leaf petioles were randomly chosen among a plot of 50 potted 3-year-old, 2m-high seed plants grown in the city of Morón (Argentina) (34º 64’ 62.61'' SL; 58º 62' 09.69'' WL). Leaves were harvested from the basal, medial, and apical parts of the plant stem (3 leaves per section) in April, and subsequently, each leaf was also divided into basal, medial, and apical sections. Leaf color, total phenol content, individual phenol composition, and DDPH radical scavenging activity were determined. Results: Petiole and leaflet color were significantly different for a* and b* values. Consequently, ΔE* was -0.12 and 0.27 for red leaf plants, but it was higher (-3.09) for red and green leaves. Interestingly, leaflets from the red leaf type had more green and yellow dyes than those of the green leaf type. Phenolic content and DPPH radical scavenging activity were significantly higher in red leaf plants (10.9 mg tannic acid and 45.6%, respectively) than in green plant leaves (9.1 mg tannic acid and 31.1%, respectively). The red leaf type had the smallest amounts of rutin and naringenin content, which were not present in the green leaf type. Nevertheless, the green leaf type showed more catechin hydrate content than the red leaf type. Conclusion: Phenolic content and antioxidant activity are modified with sampling and leaf color, so these factors must be considered as well as the selection of red leaf plants.

Background: Breast cancer is a major cause of death in women worldwide. Propolis antitumor activity has become the subject of growing research related to breast cancer. Algerian propolis is being studied for its antitumor activity on several cell lines. However, little is known about its cytotoxic activity on the human breast adenocarcinoma cell line. Objective: The present study aimed to investigate the cytotoxic effect of Algerian propolis on human breast adenocarcinoma cells (MDA-MB-231) and explain its mechanism of action. Methods: Cytotoxic activity was evaluated using an MTT assay, and mechanisms involved in the cytotoxic activity were also investigated. In addition, the chemical profile was analyzed by the determination of TP and TF contents. Results: TP and TF of the tested propolis varied between 1.36±0.15 and 97.85±2.98 GAE μg/mg for TP and 0.08±0.10 and 33.22±1,17QE μg/mg for TF. Propolis treatment of MD-MB-231 cells for 24 hours was found to suppress the growth of the tested cell line in a dose-dependent manner. The tested propolis probably induced an intrinsic pathway of apoptosis through caspase cascade and activation of pro-apoptotic proteins, such as BAX, p53, and p21. In addition, cell proliferation was found to be inhibited by the diminution of CYCLIN2 and CDK4 activities associated with the increase in P21 acting as a protein inhibitor. Conclusion: Our results demonstrated that Algerian propolis could be used as a complementary treatment for breast cancer. Our propolis was found to suppress the growth of MDA-MB-231 cells by inducing apoptosis and inhibiting cell proliferation.

Background: This study is based on ethnobotanical observation and traditional medicinal utilization of fig (Ficus carica L.) by southwest Asian and Mediterranean populations. Objective: Considering phenolics among the highly bioactive compounds for their numerous therapeutic applications, this investigation's first goal is to optimize their recovery by using Response Surface Methodology (RSM). Methods: Prior to RSM, the single-factor method was applied to reveal the main factors influencing the extraction (solvent type, solvent concentration, sample#151;to#151;solvent ratio, temperature, and time of extraction). After using the optimal conditions of extraction, the second objective was the identification of fig leave phytochemicals by UPLC#151;MS. Results: The results of the preliminary optimization step through sequential methodology revealed that solvent concentration, extraction duration, and temperature were the main influencing factors. All these tested extraction parameters significantly influenced total phenolic contents (TPC) and DPPH-free radical scavenging activity (FRSA). RSM analysis using Box#151;Behnken design showed that the optimal extraction conditions of total phenolic contents of fig leaves were 23.07% acetone, 51.82 °C, and 118.02 min with values of 29.44 mg GAE/g and 59.48% for TPC and FRSA, respectively. Eight phenolic compounds were detected, including chlorogenic, caffeic, and coumaric acids, rutin, isoquercetin, luteolin, quercetin, and kaempferol, well known for their bioactivities. Two non#151;phenolic compounds were also found: The psoralen and an oxylipin, the 9#151;oxo#151;octadecadienoic acid detected for the first time in fig leaves. Conclusion: The developed mathematical models have expressed a high level of significance through sequential and RSM optimization processes for phenolic antioxidants of Ficus carica leaves. The UPLC-MS analysis of the optimal extract revealed numerous phenolic compounds known for their bioactivities.

Aims: The study aimed to isolate and elucidate the structure of pure compounds from the polar extract of the marine sponge Desmacella sp. and explore their therapeutic potential. Background: Only a few marine organisms and their associated microorganisms collected from various parts of the Philippines have been documented and investigated in terms of their potential as sources of bioactive secondary metabolites. The sponge Desmacella sp. was collected off the coast of Agusan del Norte, Mindanao, Philippines, for the purpose of isolating compounds with medicinal prospects. Objective: The objective of the study was to explore the antibacterial, anti-inflammatory, and antidiabetic potentials of the pure isolates from the polar extract of the marine sponge Desmacella sp. Methods: The polar extract of the marine sponge Desmacella sp. from Agusan del Norte, Philippines, was subjected to purification using gravity column and medium pressure liquid chromatographic methods with TLC profiling as a guide. Pure isolates were obtained and subjected to NMR spectroscopy and mass spectrometry for structure elucidation, and the structures were confirmed by comparing the data with the literature. The pure compounds were explored for their antibacterial potential against B. subtilis BIOTECH 1679 and P. aeruginosa BIOTECH 1335 using a microplatebased antibacterial assay with resazurin indicator for the cell growth and ciprofloxacin as a positive control. Their anti-inflammatory potentials were determined using membrane stabilization and protein denaturation assays and were compared with the anti-inflammatory drug diclofenac and their antidiabetic potential by measuring their ability of inhibiting starch-hydrolyzing enzyme α-amylase. Results: The polar extract of the marine sponge Desmacella sp. from Agusan del Norte, Philippines, afforded three known compounds, namely, aaptamine, isopentylamine, and tyramine. This is the first report on the isolation of aaptamine, isopentylamine, and tyramine from the marine sponge genus Desmacella. The compounds aaptamine and isopentylamine exhibited antibacterial activity against B. subtilis, while tyramine and isopentylamine exhibited antibacterial activity against P. aeruginosa. These compounds showed the ability to inhibit heat-induced protein denaturation and effectively inhibited the erythrocytes' heat-induced hemolysis, which described in vitro antiinflammatory activity. These compounds were also evaluated for in vitro antidiabetic properties and showed their ability to inhibit the alpha-amylase enzyme activity of starch. Conclusion: Three known amines, namely, aaptamine, isopentylamine, and tyramine were isolated from the polar extract of the marine sponge Desmacella sp. collected off Mindanao coasts. Aaptamine and isopentylamine exhibited antibacterial properties against B. subtilis, while isopentylamine and tyramine exhibited antibacterial activity against P. aeruginosa. The anti-inflammatory potentials of aaptamine, isopentylamine, and tyramine were exhibited clearly in the membrane stabilization and protein denaturation assays and were compared with the anti-inflammatory drug diclofenac. Aaptamine, isopentylamine, and tyramine exhibited hypoglycemic properties and were compared with the antidiabetic drug acarbose in the inhibition of starch-hydrolyzing enzyme α-amylase assay.

Background: Ramalin (γ-glutamyl-N'-(2-hydroxyphenyl) hydrazide), a nitrogencontaining lichen secondary metabolite, was isolated from Ramalina terebrata, an Antarctic lichen. Since then, it has attracted several researchers, thus leading to various research investigations exploring the pharmacological potential of Ramalin. Methods: The bibliographic databases were explored for the peer-reviewed research related to the pharmacological importance of Ramalin. Results: The article summarizes the antioxidant, anti-cancer, anti-obesity, antibacterial, and antiallergic activities of this molecule. Additionally, the studies conducted to show the potential of Ramalin in atherosclerosis, atopic dermatitis, neurodegenerative disorders, hepatic fibrosis and its role in autophagy suppression and enzyme inhibition are also described briefly. Moreover, the experimental findings also depict that Ramalin did not show any toxicity. Conclusion: The current review shall be beneficial for future researchers interested in working on Ramalin because it summarizes all the relevant publications starting from its first-time isolation to the articles of 2021.

Scientific research in the field of veterinary pharmacology has provided new opportunities for the development of modified release dosage forms, with the aim to improve therapeutic efficacy and reduce animal stress. The formulation of classical drug molecules with advanced biomaterials has become a new approach to increasing drug bioavailability and improving the therapeutic outcome. The main reasons for the development of modified drug delivery systems for animal use are the need to reduce the animal stress caused by the handling and administration of the drug and reduce the cost in financial and chronological terms. This review discusses the most common delivery systems used in veterinary and the difficulties encountered in innovating therapeutic options in the field.

Background: Male reproductive dysfunctions are the results of the malfunctioning of one or more cellular components due to several factors, including exposure to heavy metals, reactive oxygen species, smoking and alcohol, genital infection, lifestyle, hormonal disorders, and unhealthy diet. However, it has been widely reported that curcumin possesses pharmacological potential, which could ameliorate the effects of these factors on male reproductive dysfunctions. Introduction: This review discusses the pharmacological activities of curcumin, its ameliorating effects on male reproductive dysfunction, especially on sperm disorders, steroidogenic toxicity, immune-regulatory activity, apoptotic toxicity, and oxidative toxicity, along with its possible mechanisms regarding male reproductive dysfunction. Methods: The terms, such as "Curcumin" together with "testis", "sperm", "male reproductive function", and "testosterone", were searched on Google Scholar, Pubmed, and Scopus. Relevant literature was also assessed. Results: Curcumin was found to mitigate the adverse effects on hormone levels, cellular apoptotic activity, oxidative stress, and histopathological damages. It also inhibited the activation of the mitogen-activated protein kinase (MAPK) pathway, increased semen quality, sperm motility, and concentration, and restored the IL-1β, TNF-α, and MCP-1 levels in the reproductive tissues. Furthermore, curcumin has been shown to increase mRNA, cytoplasmic Bcl-2, 3β-HSD, and 17β- HSD and Nrf2 expression, γ-GCS, and GSH-Px levels, the number of TUNEL-positive cells, and to reduce levels of LDH-x, and LDH activities. Conclusion: Curcumin exerts pharmacological activities, which improve the male reproductive functions, indicating how curcumin affects various testicular processes. This will be imperative as a measure to enhance male fertility.