Natural products, mainly plants, have a crucial role in folk medicine. Particularly, Stellera chamaejasme L. has been traditionally used in Mongolian medicine to treat various diseases, including chronic tracheitis, tuberculosis, and psoriasis. In this study, ethanol (EtOH) and dichloromethane (DCM) extracts of its roots (R) and aerial parts (AP) were evaluated for their antioxidant and anti-inflammatory activities. Thin-layer chromatography demonstrated the presence of flavonoids, namely kaempferol and quercetin-3-O-glucopyranoside, only in the EtOH-AP. Conversely, it showed that kaempferol, quercetin-3-O-glucopyranoside, coumarin, luteolin, rutin, morin, and riboflavin were not present in the other three extracts. The S. chamaejasme extracts exhibited strong antioxidant activity. In addition, the roots extracts presented the highest antioxidant activity against peroxyl radicals, with the EtOH-R being the most potent (IC₅₀ = 0.90 ± 0.07 µg/mL). S. chamaejasme extracts also efficiently inhibited the production of one of the main pro-inflammatory cytokines, interleukin (IL)-6, in a dose-dependent manner by lipopolysaccharide-stimulated macrophages. Particularly, DCM-R was the strongest extract, reducing ≈ 91.5% of the IL-6 production. Since this extract was the most effective, gas chromatography–mass spectrometry (GC-MS) analyses were performed and demonstrated the presence of two fatty acids (palmitic acid and 9-octadecenoic acid), one fatty alcohol (1-hexadecanol), and one triterpenoid (squalene) that can contribute to the observed bioactivity. Herewith, S. chamaejasme extracts, mainly DCM-R, exhibit antioxidant and anti-inflammatory activities that could be applied as new and innovative natural formulations for the treatment of chronic inflammatory diseases. Full article

The regular administration of antibiotics is a public concern due to the prejudices of large population groups and the high frequency with which antimicrobial products are prescribed. The current study aimed to evaluate the in vitro effect of a new extract from Boletus edulis (BEE) on the human microbiota. One of the disadvantages of this extensive use is the disruption of the human microbiota, leading to potential negative health consequences. The in vitro evaluation of BEE consisted in determining its cytotoxicity, influence on the concentration of four types of cytokines (IL-6, IL-10, IL-1β, TNFα), and capacity to modulate the human microbiota after administering antibiotics. The latter was assessed by microbiome analysis and the evaluation of short-chain fatty acid synthesis (SCFAs). Simultaneously, the content of total polyphenols, the antioxidant capacity, and the compositional analysis of the extract (individual polyphenols composition) were determined. The results showed that BEE modulates the microbial pattern and reduces inflammatory progression. The data demonstrated antioxidant properties correlated with the increase in synthesizing some biomarkers, such as SCFAs, which mitigated antibiotic-induced dysbiosis without using probiotic products. Full article

Chemically modified curcumin, CMC2.24, is a promising therapeutic that has shown efficacy in ameliorating excessive pigmentation in our previous studies. However, its inherent disadvantages of color, stability, solubility, and cytotoxicity to melanocytes and keratinocytes at concentrations > 4 µg/mL posed challenges in its use in cosmetic formulations. To overcome these limitations, chemical reduction by hydrogenation of CMC2.24 (compound 1) was developed to yield products at different time points of hydrogenation (1 h, 2 h, 4 h, and 24 h) referred to as partially (2, 3, 4) or fully hydrogenated (5) products, and the effects of the degree of hydrogenation on melanogenesis in vitro were explored. Compound 1 and products 2–5 were evaluated using mushroom tyrosinase activity assays with two substrates (L-tyrosine and L-DOPA), then cellular assays using B16F10 mouse melanoma cells, MNT-1 human melanoma cells, and physiological normal human melanocytes (HEMn-DP cells). The cytotoxicity, melanin contents, cellular tyrosinase activities, and cellular oxidative stress were evaluated. Moreover, the recovery of melanin contents in HEMn-DP cells was also studied. Our results provide novel insights into the role of the degree of hydrogenation of compound 1 on the biological effects of melanogenesis, which were dependent on cell type. To the best of our knowledge, this is the first study to show that in HEMn-DP cells, the anti-melanogenic efficacy of the yellow-colored CMC2.24 is retained as early as 1 h after its hydrogenation; this efficacy is enhanced with longer durations of hydrogenation, with a robust efficacy achieved for the 24 h hydrogenated product 5 at the lowest concentration of 4 µg/mL. A similar potency could be achieved for product 4 at higher concentrations, although interestingly, both differ only by a minor amount of dihydro-CMC2.24. Our results indicate promise for using products 4 & 5 as a skin-lightener in cosmetic formulations with the advantages of lack of color combined with a potency much greater than that of the parent compound 1 at lower concentrations and reversibility of the effects on melanocytes. This, along with the easy synthesis and scale-up of the hydrogenation method for CMC2.24 and the documented higher solubility, stability, and bioavailability of tetrahydrocurcumin, provides further impetus to incorporating these derivatives in cosmetic formulations. The results of this study can help to extend the therapeutic window of the lead compound CMC2.24 by providing options for selecting partially or fully hydrogenated derivatives for cosmetic applications where a trade-off between color and efficacy is needed. Thus, the degree of hydrogenation can be tuned for desired biological effects. Further studies are warranted to evaluate the efficacy of products 4 & 5 at suppressing pigmentation in 3D skin-tissue equivalents and in vivo models. Full article

Cinnamon is an evergreen and tropical plant of the family Lauraceae, growing particularly in Sri Lanka, whose aqueous extract has been tested in different studies to evaluate its possible use as an anti-cancer compound. Both in vitro and in vivo experiments seem to confirm that it acts on various cellular pathways, contributing to down-regulating the activity of molecules that stimulate the proliferation and survival of cells such as the transcription factors NF-KB and AP-1, COX-2, dihydrofolate reductase and pro-angiogenic substances such as VEGF, while up-regulating the function of immune cells against tumors, such as cytotoxic CD8+ T cells. In hematological malignancies, aqueous cinnamon extract has been studied in order to understand if it is possible to count on its help, alone or in combination with traditional drugs such as doxorubicin, to treat patients. The aim of our work is to investigate results from in vitro and in vivo studies about the possible anti-cancer effect of aqueous cinnamon extract in hematological malignancies and the different pathways involved in its action. The possibility of using cinnamon extract in clinical practice is discussed; even if its use could appear very interesting, more studies are necessary to clear the real potentiality of this substance in cancer. Full article

Aberrant accumulation of the neurotransmitter L-glutamate (L-Glu) has been implicated as a mechanism of neurodegeneration, and the release of L-Glu after stroke onset leads to a toxicity cascade that results in neuronal death. The acai berry (Euterpe oleracea) is a potential dietary nutraceutical. The aim of this research was to investigate the neuroprotective effects of acai berry aqueous and ethanolic extracts to reduce the neurotoxicity to neuronal cells triggered by L-Glu application. L-Glu and acai berry effects on cell viability were quantified using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays, and effects on cellular bioenergetics were assessed via quantitation of the levels of cellular ATP, mitochondrial membrane potential (MMP), and production of reactive oxygen species (ROS) in neuroblastoma cells. Cell viability was also evaluated in human cortical neuronal progenitor cell culture after L-Glu or/and acai berry application. In isolated cells, activated currents using patch-clamping were employed to determine whether L-Glu neurotoxicity was mediated by ionotropic L-Glu-receptors (iGluRs). L-Glu caused a significant reduction in cell viability, ATP, and MMP levels and increased ROS production. The co-application of both acai berry extracts with L-Glu provided neuroprotection against L-Glu with sustained cell viability, decreased LDH production, restored ATP and MMP levels, and reduced ROS levels. Whole-cell patch-clamp recordings showed that L-Glu toxicity is not mediated by the activation of iGluRs in neuroblastoma cells. Fractionation and analysis of acai berry extracts with liquid chromatography-mass spectrometry identified several phytochemical antioxidants that may have provided neuroprotective effects. In summary, the acai berry contains nutraceuticals with antioxidant activity that may be a beneficial dietary component to limit pathological deficits triggered by excessive L-Glu accumulations. Full article

The study aimed to characterize the consequences of a 15-week intake of 10% fructose on the kidney, with the focus on oxidative stress markers and properties of the Na,K-ATPase enzyme. Various antioxidants naturally occurring in common food were demonstrated to be protective against fructose-induced deterioration of kidneys. Therefore, we also aimed to observe the effect of 6-week quercetin administration (20 mg/kg/day) that was initiated following the 9-week period of higher fructose intake, by determining the concentration of sodium, potassium, creatinine, urea, and glucose in blood plasma and oxidative status directly in the renal tissue. Kinetic studies of renal Na,K-ATPase were utilized for a deeper insight into the molecular principles of expected changes in this enzyme activity under conditions of presumed fructose-induced renal injury. Fructose intake led to increase in body weight gain, plasma glucose and sodium levels, and deterioration of kidney properties, although some compensatory mechanisms were observable. Quercetin administration improved glycemic control in rats exposed to fructose overload. However, an increase in plasma creatinine, a decrease in GSH/GSSG ratio in renal tissue homogenate, and a controversial effect on renal Na,K-ATPase enzyme suggest that quercetin treatment may not be beneficial in the condition of pre-existing renal pathology. Full article

Arthrospira platensis is a filamentous cyanobacterium of the class Cyanophyceae and is the most cultivated photosynthetic prokaryote. It is used in the pharmaceutical sector, medicine and the food industry. It has a rich micro- and macro-element composition, containing proteins, lipids, carbohydrates, essential amino acids, polyunsaturated fatty acids, minerals and raw fibers. It is a commonly used ingredient in food products and nutritional supplements. The wide range of biologically active components determines its diverse pharmacological properties (antioxidant, antidiabetic, antimicrobial, antineoplastic, antitumor, anti-inflammatory, photoprotective, antiviral, etc.). This review summarizes research related to the taxonomy, distribution and chemical composition of Arthrospira platensis as well as its potential application in the food and pharmaceutical industries. Attention is drawn to its various medical applications as an antidiabetic and antiobesity agent, with hepatoprotective, antitumor, antimicrobial and antiviral effects as well as regulatory effects on neurodegenerative diseases. Full article

Artemisia annua (AA) is an aromatic plant belonging to the Asteraceae family, which has long been known for its several medicinal virtues. In addition, essential oils (EOs) extracted from AA have a wide range of therapeutic properties. Therefore, this study aimed to investigate the phytochemical composition, anti-microbial, and anti-oxidant properties of Artemisia annua essential oil (EOAA). EO was extracted, and its chemical constituents were ascertained by the use of GC-MS analysis. EOAA shows remarkable antioxidant capacities of DPPH free radical scavenging with an IC₅₀ value of 29 ± 5.3 μg/mL and ferric reducing antioxidant power with an EC₅₀ value of 9.21 ± 0.3 µg/mL, and it also has a good total antioxidant capacity of 911.59 ± 115.71 milligrams of ascorbic acid equivalence per gram of EO (mg AAE/g EO). Moreover, the in vitro antimicrobial screening results indicate that EOAA has shown promising antibacterial activity, especially against the Escherichia coli strain, and it also shows significant antifungal activity against Fusarium oxysporum and Candida albicans yeasts. Taken together, our findings highlight the importance of EOAA as a source of strong antioxidant and antimicrobial agents, which could be used as an alternative form to control free radicals and combat drug-resistant microbes. Full article

The present study investigated the antioxidant and antimicrobial activities as well as characterized the chemical composition of the essential oils (EO) isolated from Artemisia flahaultii (EOF). EOF was extracted using hydro-distillation, and the chemical composition of EOF was ascertained by gas chromatography coupled with mass spectrometry (GC/MS). To assess antioxidant capacity, three tests were used: the 2,2-diphenyl-1-picrylhydrazil (DPPH), the total antioxidant capacity (TAC) and the ferric-reducing antioxidant power (FRAP) test. The antimicrobial activity of EOF was investigated using the diffusion assay and minimal inhibitory concentration assays (MICs). By use of in silico structure–activity simulations, the inhibitory potency against nicotinamide adenine dinucleotide phosphate (NADPH), physicochemical characters, pharmaco-centric properties and absorption, distribution, metabolism, excretion (ADME) characteristics of EOF were determined. GC/MS analysis reveals 25 components majorly composed of D-Limonene (22.09%) followed by β-pinene (15.22%), O-cymene (11.72%), β-vinylnaphthalene (10.47%) and benzene 2,4-pentadiynyl (9.04%). The capacity of DPPH scavenging by EOF scored an IC50 of 16.00 ± 0.20 µg/mL. TAC revealed that the examined oils contained considerable amounts of antioxidants, which were determined to be 1094.190 ± 31.515 mg ascorbic acid equivalents (AAE)/g EO. Results of the FRAP method showed that EOF exhibited activity with EC50 = 6.20 ± 0.60 µg/mL. Values for minimal inhibitory concentration (MIC) against certain clinically important pathogenic bacteria demonstrate EOF’s potent antibacterial activity. MIC values of 1.34, 1.79, and 4.47 μg/mL against E. coli, B. subtilis and S. aureus were observed respectively. EOF exhibited significant antifungal activities against two stains of fungi: F. oxysporum and C. albicans, with values of 10.70 and 2.23 μg/mL, respectively. Of the total, 25 essential oils were identified. 2,4-Di-tert-butylphenol and capillin were the most active molecules against NADPH. The ADME prediction revealed that EOF was characterized by useful physicochemical characteristics and pharmaco-centric properties. The findings of this study show that the EOF can be used as an alternative to treat microbial resistance. Based on the in silico studies, EOF can be used as an “eco-friendly” NADPH inhibitor. Full article

The genus Kalanchoe Adans. (Crassulaceae) is native to Madagascar and comprises 145 species, being naturalized in the tropics and cultivated worldwide. In addition to having ornamental value, several Kalanchoe species are commonly used in popular medicine for the treatment of inflammatory conditions, wounds, gastric ulcers, and other diseases. The great importance of the genus is reflected on its acknowledgment by traditional and alternative health systems and organizations, as well as on the growing number of papers reporting pharmacological properties of extracts and isolated compounds from Kalanchoe. Among these properties, we highlight anti-inflammatory, antitumor, wound healing, antiulcer, and muscle relaxing properties. These activities are attributed mostly to flavonoids and bufadienolides, the main secondary metabolites reported in Kalanchoe extracts. While bufadienolides are generally related to cytotoxic and muscle relaxing activities, flavonoids are commonly reported as anti-inflammatory and wound healing agents. This review provides up to date information and perspectives on bioactive compounds from the Kalanchoe genus that are potentially useful for the development of new drugs. It includes not only a discussion on the advantages of the Kalanchoe species as source of bioactive compounds, but also the gaps, opportunities, and challenges to translate the acquired knowledge into innovation for drug development. Full article

TRAIL (Tumor necrosis factor–Related Apoptosis-Inducing Ligand) has the ability to selectively kill cancer cells without being toxic to normal cells. This endogenous ligand plays an important role in surveillance and anti-tumor immunity. However, numerous tumor cells are resistant to TRAIL-induced apoptosis. In this study, the apoptotic effect of santin in combination with TRAIL on colon cancer cells was examined. Flow cytometry was used to detect the apoptosis and expression of death receptors (TRAIL-R1/DR4 and TRAIL-R2/DR5). Mitochondrial membrane potential (ΔΨm) was evaluated by DePsipher staining with the use of fluorescence microscopy. We have shown for the first time that flavonoid santin synergizes with TRAIL to induce apoptosis in colon cancer cells. Santin induced TRAIL-mediated apoptosis through increased expression of death receptors TRAIL-R1 and TRAIL-R2 and augmented disruption of the mitochondrial membrane in SW480 and SW620 cancer cells. The obtained data may indicate the potential role of santin in colon cancer chemoprevention through the enhancement of TRAIL-mediated apoptosis. Full article

Sorbaria pallasii is an endemic species of the Far East and Siberia and grows along the Goltsy altitudinal belt. Data on micropropagation and phytochemical characteristics of this plant are not available, probably because of the inaccessibility of the plant material. Morphogenesis initiation from flower buds of S. pallasii in vitro and micropropagation were performed here in the Murashige and Skoog medium supplemented with 5.0 µM 6-benzylaminopurine and 0.0–1.0 µM α-naphthylacetic acid; elongation was implemented in the same medium without the hormones. A well-growing sterile culture of S. pallasii was obtained; the number of microshoots per explant reached 5.7 ± 1.2. Phytochemical analyses of in vitro propagated S. pallasii detected 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity in a water-ethanol extract from its microshoots and revealed phenolic compounds in it. The phenolic compounds that likely contribute to its biological activity are tannins (74.9 mg/g), phenolcarboxylic acids (30.8 mg/g), and catechins (13.3 mg/g). In the microshoot extract, high-performance liquid chromatography identified three catechins. Microshoots showed the highest concentration of (±)-catechin (3.03 mg/(g of absolutely dry mass; ADM)). Concentrations of epigallocatechin gallate (0.38 mg/(g of ADM)) and (−)-epicatechin (0.55 mg/(g of ADM)) were significantly lower. This study paves the way for further biotechnological and phytochemical research on S. pallasii. Full article

The aim of the study is to investigate whether the bioactive compounds isolated from P. lanceolata inflorescences, namely, phenylethanoid glucosides, acteoside, plantamajoside, and a flavonoid, isorhamnetin-3-O-rutinoside-4′-O-glucoside, possessed cytotoxic activity against the selected cancer cell lines. The potential antitumor effects of two phenylethanoid glycosides and one flavonoid were evaluated via MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay on seven human carcinoma cell lines (MCF-7, MDA-MB-231, Caco-2, HepG2, OVCAR-3, U138-MG, U251-MG) and one nontumorigenic mammary epithelial cell line (MCF-12A). For the first time, acteoside was studied in ovarian cancer cell line OVCAR-3, and plantamajoside in all cell lines except breast adenocarcinoma MDA-MB-281 and hepatocarcinoma HepG2. The phenylethanoid glycosides showed stronger cytotoxic activity than that of the glycoside flavonoid. Acteoside and plantamajoside, at concentrations of 200 and 300 μM, respectively, had a highly toxic effect on the selected two cancer cell lines of breast adenocarcinoma MDA-MB-231 and MCF-7, ovarian cancer cell line OVCAR-3, glioblastoma cell line U138-MG, and hepatocarcinoma cell line HepG2. Both glycosides were significantly less cytotoxic towards nontumorigenic cell line MCF-12A; the effect appeared at a concentration of 400 μM. For the first time, the activity of acteoside and plantamajoside was compared in one parallel investigation. The results are discussed against a broad background of existing knowledge on biological effects, their mechanisms, and structure–activity relationships. Phenylethanoids may be potential compounds with cytotoxic activity against the selected cancer types. Full article

Recently, due to the decreasing areas of cultivation and climate change, the use of biotechnological methods to obtain biomass, which is a source of valuable bioactive metabolites, is becoming more and more interesting. In this study, Ruta chalepensis in vitro cultures were investigated in RITA^® temporary immersion bioreactors. Biomass growth and the production of secondary metabolites in 4- and 5-week growth cycles on three variants of the Linsmaier and Skoog (LS) medium (naphthyl-1-acetic acid/6-benzylaminopurine (NAA/BAP): 0.5/1.0, 0.1/0.1, and 1.0/1.0 mg/L) were analyzed. Using high-performance liquid chromatography of methanolic extracts of biomass, the presence of linear furanocoumarins (bergapten, isoimperatorin, isopimpinellin, psoralen, and xanthotoxin) and furoquinoline alkaloids (γ-fagarine, 7-isopentenyloxy-γ-fagarine, and skimmianine) was confirmed. The highest content of linear furanocoumarins (1170 mg/100 g DW (dry weight)) was observed in the LS medium variant containing 0.5/1.0 mg/L NAA/BAP (4-week growth cycle). The highest content of furoquinoline alkaloids (449 mg/100 g DW) was observed in the LS medium variant containing 0.1/0.1 mg/L NAA/BAP (5-week growth cycle). Hence, R. chalepensis bioreactor cultures may be used as a biotechnological source of linear furanocoumarins (xanthotoxin and bergapten) and furoquinoline alkaloids (skimmianine and γ-fagarine). Full article

Acacia Nilotica (AN) has long been used as a folk cure for asthma, but little is known about how AN could possibly modulate this disease. Thus, an in-silico molecular mechanism for AN’s anti-asthmatic action was elucidated utilizing network pharmacology and molecular docking techniques. DPED, PubChem, Binding DB, DisGeNET, DAVID, and STRING were a few databases used to collect network data. MOE 2015.10 software was used for molecular docking. Out of 51 searched compounds of AN, eighteen compounds interacted with human target genes, a total of 189 compounds-related genes, and 2096 asthma-related genes were found in public databases, with 80 overlapping genes between them. AKT1, EGFR, VEGFA, and HSP90AB were the hub genes, whereas quercetin and apigenin were the most active components. p13AKT and MAPK signaling pathways were found to be the primary target of AN. Outcomes of network pharmacology and molecular docking predicted that AN might exert its anti-asthmatic effect probably by altering the p13AKT and MAPK signaling pathway. Full article

The present work aimed to detail the mechanisms elicited by Allophylus africanus P. Beauv. stem bark extract in human stomach cancer cells and to identify the bioactives underlying the cytotoxicity. MTT reduction and LDH leakage assays allowed characterizing the cytotoxic effects in AGS cells, which were further detailed by morphological analysis using phalloidin and Hoechst 33258. Proapoptotic mechanisms were elucidated through a mitochondrial membrane potential assay and by assessing the impact upon the activity of caspase-9 and -3. The extract displayed selective cytotoxicity against AGS cells. The absence of plasma membrane permeabilization, along with apoptotic body formation, suggested that pro-apoptotic effects triggered cell death. Intrinsic apoptosis pathway activation was verified, as mitochondrial membrane potential decrease and activation of caspase-9 and -3 were observed. HPLC-DAD profiling enabled the identification of two apigenin-di-C-glycosides, vicenin-2 (1) and apigenin-6-C-hexoside-8-C-pentoside (3), as well as three mono-C-glycosides-O-glycosylated derivatives, apigenin-7-O-hexoside-8-C-hexoside (2), apigenin-8-C-(2-rhamnosyl)hexoside (4) and apigenin-6-C-(2-rhamnosyl)hexoside (5). Isovitexin-2″-O-rhamnoside (5) is the main constituent, accounting for nearly 40% of the total quantifiable flavonoid content. Our results allowed us to establish the relationship between the presence of vicenin-2 and other apigenin derivatives with the contribution to the cytotoxic effects on the presented AGS cells. Our findings attest the anticancer potential of A. africanus stem bark against gastric adenocarcinoma, calling for studies to develop herbal-based products and/or the use of apigenin derivatives in chemotherapeutic drug development. Full article

Among the many factors inducing prostate inflammation, bacterial contribution is potentially underrated according to the scientific community. Bacterial prostatitis is characterized by modifications of the prostatic microenvironment, mainly driven by the immune system. Macrophages play a major role in bacterial prostatitis, secreting a plethora of proinflammatory and chemoattractive cytokines and proteolytic enzymes able to degrade the ECM, so facilitating the invasion of other immune cells. Consequently, macrophages represent a link between bacterial infection and prostate inflammation, as well as being the main target of prostate anti-inflammatory drugs and dietary supplements. This study aims to investigate the effect of a formulation composed of active principles and a probiotic strain with a particular focus on the anti-inflammatory effect in an in vitro bacterial prostatitis model. The results obtained showed that the formulation reduces the inflammatory response of prostatic epithelium induced by bacterial infection. This effect is mediated by the modulation of activated macrophages. Analysis of the cytokines released highlights that the tested formulation is able to reduce the expression of key proinflammatory cytokines involved in the pathogenesis of prostate diseases, in particular prostate cancer, and represents a valuable tool to prevent bacterial prostatitis and ensure favorable prostate health. Full article

The recent pandemic of COVID-19 caused by the SARS-CoV-2 virus has brought upon the world an unprecedented challenge. During its acute dissemination, a rush for vaccines started, making the scientific community come together and contribute to the development of efficient therapeutic agents and vaccines. Natural products have been used as sources of individual molecules and extracts capable of inhibiting/neutralizing several microorganisms, including viruses. Natural extracts have shown effective results against the coronavirus family, when first tested in the outbreak of SARS-CoV-1, back in 2002. In this review, the relationship between natural extracts and SARS-CoV is discussed, while also providing insight into misinformation regarding the use of plants as possible therapeutic agents. Studies with plant extracts on coronaviruses are presented, as well as the main inhibition assays and trends for the future regarding the yet unknown long-lasting effects post-infection with SARS-CoV-2. Full article

In this study, phytochemicals extracted from three different Achillea genera were identified and analyzed to be screened for their interactions with the SARS-CoV-2 main protease. In particular, the antiviral potential of these natural products against the SARS-CoV-2 main protease was investigated, as was their effectiveness against the SARS-CoV-1 main protease as a standard (due to its high similarity with SARS-CoV-2). These enzymes play key roles in the proliferation of viral strains in the human cytological domain. GC-MS analysis was used to identify the essential oils of the Achillea species. Chemi-informatics tools, such as AutoDock 4.2.6, SwissADME, ProTox-II, and LigPlot, were used to investigate the action of the pharmacoactive compounds against the main proteases of SARS-CoV-1 and SARS-CoV-2. Based on the binding energies of kessanyl acetate, chavibetol (m-eugenol), farnesol, and 7-epi-β-eudesmol were localized at the active site of the coronaviruses. Furthermore, these molecules, through hydrogen bonding with the amino acid residues of the active sites of viral proteins, were found to block the progression of SARS-CoV-2. Screening and computer analysis provided us with the opportunity to consider these molecules for further preclinical studies. Furthermore, considering their low toxicity, the data may pave the way for new in vitro and in vivo research on these natural inhibitors of the main SARS-CoV-2 protease. Full article

The fruits, leaves, and bark of the guava (Psidium guajava) tree have traditionally been used to treat a myriad of ailments, especially in the tropical and subtropical regions. The various parts of the plant have been shown to exhibit medicinal properties, such as antimicrobial, antioxidant, anti-inflammatory, and antidiabetic activities. Recent studies have shown that the bioactive phytochemicals of several parts of the P. guajava plant exhibit anticancer activity. This review aims to present a concise summary of the in vitro and in vivo studies investigating the anticancer activity of the plant against various human cancer cell lines and animal models, including the identified phytochemicals that contributes to their activity via the different mechanisms. In vitro growth and cell viability studies, such as the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the sulforhodamine B (SRB) assay, and the trypan blue exclusion test, were conducted using P. guajava extracts and their biomolecules to assess their effects on human cancer cell lines. Numerous studies have showcased that the P. guajava plant and its bioactive molecules, especially those extracted from its leaves, selectively suppress the growth of human cancer cells without cytotoxicity against the normal cells. This review presents the potential of the extracts of P. guajava and the bioactive molecules derived from it, to be utilized as a feasible alternative or adjuvant treatment for human cancers. The availability of the plant also contributes towards its viability as a cancer treatment in developing countries. Full article

Banana ranks as the fifth most cultivated agricultural crop globally, highlighting its crucial socio-economic role. The banana’s health-promoting benefits are correlated with its composition in bioactive compounds, such as phenolic compounds. Thus, the present study attempts to evaluate the potential health benefits of banana phenolic content by combing analytical and in silico techniques. Particularly, the total phenolic content and antioxidant/antiradical activity of banana samples during ripening were determined spectrophotometrically. In parallel, liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was implemented to unravel the variations in the phenolic profile of banana samples during ripening. Chlorogenic acid emerged as a ripening marker of banana, while apigenin and naringenin were abundant in the unripe fruit. In a further step, the binding potential of the elucidated phytochemicals was examined by utilizing molecular target prediction tools. Human carbonic anhydrase II (hCA-II) and XII (hCA-XII) enzymes were identified as the most promising targets and the inhibitory affinity of phenolic compounds was predicted through molecular docking studies. This class of enzymes is linked to a variety of pathological conditions, such as edema, obesity, hypertension, cancer, etc. The results assessment indicated that all assigned phenolic compounds constitute great candidates with potential inhibitory activity against CA enzymes. Full article

The skin serves as the body’s first line of defense, guarding against mechanical, chemical, and thermal damage to the interior organs. It includes a highly developed immune response that serves as a barrier against pathogenic infections. Wound healing is a dynamic process underpinned by numerous cellular activities, including homeostasis, inflammation, proliferation, and remodeling, that require proper harmonious integration to effectively repair the damaged tissue. Following cutaneous damage, microorganisms can quickly enter the tissues beneath the skin, which can result in chronic wounds and fatal infections. Natural phytomedicines that possess considerable pharmacological properties have been widely and effectively employed forwound treatment and infection prevention. Since ancient times, phytotherapy has been able to efficiently treat cutaneous wounds, reduce the onset of infections, and minimize the usage of antibiotics that cause critical antibiotic resistance. There are a remarkable number of wound-healing botanicals that have been widely used in the Northern Hemisphere, including Achiella millefolium, Aloe vera, Althaea officinalis, Calendula officinalis, Matricaria chamomilla, Curcuma longa, Eucalyptus, Jojoba, plantain, pine, green tea, pomegranate, and Inula. This review addresses the most often used medicinal plants from the Northern Hemisphere that facilitate the treatment of wounds, and also suggests viable natural alternatives that can be used in the field of wound care. Full article

Sunitinib has been associated with several cardiotoxic effects such as cardiac fibrosis. The present study was designed to explore the role of interleukin (IL)-17 in sunitinib-induced myocardial fibrosis (MF) in rats and whether its neutralization and/or administration of black garlic (BG), a form of fermented raw garlic (Allium sativum L.), could extenuate this adverse effect. Male Wistar albino rats received sunitinib (25 mg/kg three times a week, orally) and were co-treated with secukinumab (3 mg/kg, subcutaneously, three times total) and/or BG (300 mg/kg/day, orally) for four weeks. Administration of sunitinib induced significant increase in cardiac index, cardiac inflammatory markers, and cardiac dysfunction that were ameliorated by both secukinumab and BG, and to a preferable extent, with the combined treatment. Histological examination revealed disruption in the myocardial architecture and interstitial fibrosis in cardiac sections of the sunitinib group, which were reversed by both secukinumab and BG treatments. Both drugs and their co-administration restored normal cardiac functions, downregulated cardiac inflammatory cytokines, mainly IL-17 and NF-κB, along with increasing the MMP1/TIMP1 ratio. Additionally, they attenuated sunitinib-induced upregulation of the OPG/RANK/RANKL axis. These findings highlight another new mechanism through which sunitinib can induce interstitial MF. The current results propose that neutralizing IL-17 by secukinumab and/or supplementation with BG can be a promising therapeutic approach for ameliorating sunitinib-induced MF. Full article

Microbial infections are by no means a health problem from a past era due to the increasing antimicrobial resistance of infectious strains. Medicine is in constant need of new drugs and, recently, plant products have had a deserved renaissance and garnered scientific recognition. The aim of this work was to assess the antimicrobial activity of ten active ingredients from four Hypericum species growing in Bulgaria, as well as to obtain preliminary data on the phytochemical composition of the most promising samples. Extracts and fractions from H. rochelii Griseb. ex Schenk, H. hirsutum L., H. barbatum Jacq. and H. rumeliacum Boiss. obtained with conventional or supercritical CO₂ extraction were tested on a panel of pathogenic microorganisms using broth microdilution, agar plates, dehydrogenase activity and biofilm assays. The panel of samples showed from weak to extraordinary antibacterial effects. Three of them (from H. rochelii and H. hirsutum) had minimum inhibitory concentrations as low as 0.625–78 mg/L and minimum bactericidal concentrations of 19.5–625 mg/L against Staphylococcus aureus and other Gram-positive bacteria. These values placed these samples among the best antibacterial extracts from the Hypericum genus. Some of the agents also demonstrated very high antibiofilm activity against methicillin-resistant S. aureus. Ultra-high-performance liquid chromatography–high-resolution mass spectrometry revealed the three most potent samples as rich sources of biologically active phloroglucinols. They were shown to be good drug or nutraceutical candidates, presumably without some of the side effects of conventional antibiotics. Full article

Colorectal cancer (CRC) is one of the most common cancers worldwide. Its main modifiable risk factors are diet, alcohol consumption, and smoking. Thus, the right approach through lifestyle changes may lead to its prevention. In fact, some natural dietary components have exhibited chemopreventive activity through modulation of cellular processes involved in CRC development. Although cancer is a multi-factorial process, the study of post-translational modifications (PTMs) of proteins associated with CRC has recently gained interest, as inappropriate modification is closely related to the activation of cell signalling pathways involved in carcinogenesis. Therefore, this review aimed to collect the main PTMs associated with CRC, analyse the relationship between different proteins that are susceptible to inappropriate PTMs, and review the available scientific literature on the role of plant-based dietary compounds in modulating CRC-associated PTMs. In summary, this review suggested that some plant-based dietary components such as phenols, flavonoids, lignans, terpenoids, and alkaloids may be able to correct the inappropriate PTMs associated with CRC and promote apoptosis in tumour cells. Full article

Plant-derived bioactive compounds are gaining wide attention for their multiple health-promoting activities and in particular for their anti-cancer properties. Several studies have highlighted how they can prevent cancer initiation and progression, improve the effectiveness of chemotherapy, and, in some cases, limit some of the side effects of chemotherapy agents. In this paper, we provide an update of the literature on the anti-cancer effects of three extensively studied plant-derived compounds, namely resveratrol, epigallocatechin gallate, and curcumin, with a special focus on the anti-cancer molecular mechanisms inducing apoptosis in the major types of cancers globally. Full article

Seeds’ abundant biologically active compounds make them a suitable primary platform for the production of natural extracts, innovative foods, medicines, and cosmetics. High levels of industrial and agricultural residues and byproducts are generated during the processing of grapes, although some parts can also be repurposed. This paper examines the phytochemical composition, manufacturing processes, and health-improving attributes of many varieties of grape oil derived using various extraction methods. Since the results are influenced by a range of factors, they are expressed differently among studies, and the researchers employ a variety of measuring units, making it difficult to convey the results. The primary topics covered in most papers are grape seed oil’s lipophilic fatty acids, tocopherols, and phytosterols. In addition, new methods for extracting grape seed oil should therefore be designed; these methods must be affordable, energy-efficient, and environmentally friendly in order to increase the oil’s quality by extracting bioactive components and thereby increasing its biological activity in order to become part of the overall management of multiple diseases. Full article

Oxidative stress is one of the key factors responsible for many diseases–neurodegenerative (Parkinson and Alzheimer) diseases, diabetes, atherosclerosis, etc. Creatine, a natural amino acid derivative, is capable of exerting mild, direct antioxidant activity in cultured mammalian cells acutely injured with an array of different reactive oxygen species (ROS) generating compounds. The aim of the study was in vitro (on isolated rat brain sub-cellular fractions–synaptosomes, mitochondria and microsomes) evaluation of newly synthetized creatine derivatives for possible antioxidant and neuroprotective activity. The synaptosomes and mitochondria were obtained by multiple centrifugations with Percoll, while microsomes–only by multiple centrifugations. Varying models of oxidative stress were used to study the possible antioxidant and neuroprotective effects of the respective compounds: on synaptosomes–6-hydroxydopamine; on mitochondria–tert-butyl hydroperoxide; and on microsomes–iron/ascorbate (non-enzyme-induced lipid peroxidation). Administered alone, creatine derivatives and creatine (at concentration 38 µM) revealed neurotoxic and pro-oxidant effects on isolated rat brain subcellular fractions (synaptosomes, mitochondria and microsomes). In models of 6-hydroxydopamine (on synaptosomes), tert-butyl hydroperoxide (on mitochondria) and iron/ascorbate (on microsomes)-induced oxidative stress, the derivatives showed neuroprotective and antioxidant effects. These effects may be due to the preservation of the reduced glutathione level, ROS scavenging and membranes’ stabilizers against free radicals. Thus, they play a role in the antioxidative defense system and have a promising potential as therapeutic neuroprotective agents for the treatment of neurodegenerative disorders, connected with oxidative stress, such as Parkinson’s disease. Full article

Osteoarthritis (OA) is the most common degenerative joint disease characterized by enzymatic degradation of the cartilage extracellular matrix (ECM) causing joint pain and disability. There is no disease-modifying drug available for the treatment of OA. An ideal drug is expected to stop cartilage ECM degradation and restore the degenerated ECM. The ECM primarily contains type II collagen and aggrecan but also has minor quantities of other collagen fibers and proteoglycans. In OA joints, the components of the cartilage ECM are degraded by matrix-degrading proteases and hydrolases which are produced by chondrocytes and synoviocytes. Matrix metalloproteinase-13 (MMP-13) and a disintegrin and metalloproteinase with thrombospondin motifs 4 and 5 (ADAMTS5) are the major collagenase and aggrecanase, respectively, which are highly expressed in OA cartilage and promote cartilage ECM degradation. Current studies using various in vitro and in vivo approaches show that natural compounds inhibit the expression and activity of MMP-13, ADAMTS4, and ADAMTS5 and increase the expression of ECM components. In this review, we have summarized recent advancements in OA research with a focus on natural compounds as potential therapeutics for the treatment of OA with emphasis on the prevention of cartilage ECM degradation and improvement of joint health. Full article

Thymoquinone (TQ), an active constituent of Nigella sativa, has been reported to exert a broad spectrum of pharmacological effects, including neuroprotective, anticancer, anti-inflammatory, antidiabetic, antiepileptic, antioxidant, and other modulatory roles in inflammation in experimental studies. The present study aims to evaluate the potential effects of TQ on vincristine-induced neuropathy in mice, as well as the possible role of oxidative stress, and pro- and anti-inflammatory cytokine in neuropathy development. A Swiss strain of male albino mice were randomly divided into seven groups, comprising of five animals each. Vincristine sulfate (0.1 mg/kg, i.p.) was administered for 10 consecutive days for the induction of peripheral neuropathy. The animals received their respective treatment of TQ (2.5, 5, and 10 mg/kg, p.o.) and pregabalin (10 mg/kg, p.o.) concurrently with vincristine for 10 days followed by 4 days post treatment. The animals were assessed for pain and related behavior on day 7 and 14 using hot and cold plates, and a rotarod test. TQ preventive treatment attenuated vincristine induced neuropathy in a dose dependent manner evidenced as a significant (p < 0.001) increase in reaction time on the hot plate and the cold plate, and a fall off time on the rotarod test. Further, TQ preventive treatment resulted in a significant (p < 0.001) reduction in the number of flinches and duration of paw elevation in a formalin test. Preventative treatment with TQ abolished the vincristine-induced rise in malondialdehyde and glutathione depletion in sciatic nerve tissue, as well as the blood IL-6 levels. In conclusion, TQ at 2.5, 5, and 10 mg/kg dose produced significant attenuation of neuropathic pain induced by vincristine which may be due to its antinociceptive, antioxidant, and anti-proinflammatory activity. Full article

Eye health is crucial, and the onset of diseases can reduce vision and affect the quality of life of patients. The main causes of progressive and irreversible vision loss include various pathologies, such as cataracts, ocular atrophy, corneal opacity, age-related macular degeneration, uncorrected refractive error, posterior capsular opacification, uveitis, glaucoma, diabetic retinopathy, retinal detachment, undetermined disease and other disorders involving oxidative stress and inflammation. The eyes are constantly exposed to the external environment and, for this reason, must be protected from damage from the outside. Many drugs, including cortisonics and antinflammatory drugs have widely been used to counteract eye disorders. However, recent advances have been obtained via supplementation with natural antioxidants and nutraceuticals for patients. In particular, evidence has accumulated that polyphenols (mostly deriving from Citrus Bergamia) represent a reliable source of antioxidants able to counteract oxidative stress accompanying early stages of eye diseases. Luteolin in particular has been found to protect photoreceptors, thereby improving vision in many disease states. Moreover, a consistent anti-inflammatory response was found to occur when curcumin is used alone or in combination with other nutraceuticals. Additionally, Coenzyme Q10 has been demonstrated to produce a consistent effect in reducing ocular pressure, thereby leading to protection in patients undergoing glaucoma. Finally, both grape seed extract, rich in anthocyanosides, and polynsatured fatty acids seem to contribute to the prevention of retinal disorders. Thus, a combination of nutraceuticals and antioxidants may represent the right solution for a multi-action activity in eye protection, in association with current drug therapies, and this will be of potential interest in early stages of eye disorders. Full article

The present work was designed to study the chemical composition, antioxidant, antihyperglycemic effect, and toxicity assessment of Ridolfia segetum (L.) Moris extract. The chemical composition was studied by use of high-performance liquid chromatography (HPLC). Antioxidant power was tested by use of DPPH and FRAP assays. The antihyperglycemic effect was tested by use of a glucose tolerance test, while toxicity assessment was done in vivo by use of Wistar rats for 14 days. Analysis of the extract by HPLC-UV revealed the presence of gallic acid, catechol, vanillic acid, catechin, tannic acid, rosmarinic acid, naringenin, and coumarin acid. The crude hydroethanolic extract possessed high levels of total phenols (15.6 ± 1.76 mg EAG/g), condensed tannins (383.49 mg ECat/g DM), and flavonoid (11.63 mg EQ/g). The findings showed that the studied extract possessed good antioxidant power with IC₅₀ values equal to 550, 650, 700 µg/mL respectively for the decoction, the ethyl acetate fraction (F_2M), and the ethyl acetate fraction (F_2E). For the antioxidant activity by FRAP, the aqueous fraction (F_3E) and the aqueous extract (F₄) showed CE₅₀ values of 0.33 mg/mL and 0.4 mg/mL, respectively. Glucose tolerance test analysis showed that R. segetum (L.) Moris decoction had a significant postprandial antihyperglycemic effect in normal Wistar rats. The results of the acute toxicity test showed that the decoction was not toxic even at 2 g/Kg. Pancreatic α-amylase activity was significantly inhibited in the presence of R. segetum (L.) Moris extract (IC₅₀ = 0.133 ± 0.09 mg/mL). The outcome of the present work showed that R. segetum (L.) Moris is very rich in phenolic compounds with potent antioxidant and antihyperglycemic effects. Full article

Complementary alternative medicine approaches are growing treatments of diseases to standard medicine practice. Many of these concepts are being adopted into standard practice and orthomolecular medicine. Age-related diseases, in particular neurodegenerative disorders, are particularly difficult to treat and a cure is likely a distant expectation for many of them. Shifting attention from pharmaceuticals to phytoceuticals and “bugs as drugs” represents a paradigm shift and novel approaches to intervention and management of age-related diseases and downstream effects of aging. Although they have their own unique pathologies, a growing body of evidence suggests Alzheimer’s disease (AD) and vascular dementia (VaD) share common pathology and features. Moreover, normal metabolic processes contribute to detrimental aging and age-related diseases such as AD. Recognizing the role that the cerebral and cardiovascular pathways play in AD and age-related diseases represents a common denominator in their pathobiology. Understanding how prosaic foods and medications are co-metabolized with the gut microbiota (GMB) would advance personalized medicine and represents a paradigm shift in our view of human physiology and biochemistry. Extending that advance to include a new physiology for the advanced age-related diseases would provide new treatment targets for mild cognitive impairment, dementia, and neurodegeneration and may speed up medical advancements for these particularly devastating and debilitating diseases. Here, we explore selected foods and their derivatives and suggest new dementia treatment approaches for age-related diseases that focus on reexamining the role of the GMB. Full article

The administration of chokeberry extract in vitro in the GIS1 system was evaluated for the modulation capacity of the dysbiotic pattern resulting from the consumption of stevia. The microbial pattern determined by molecular method, the metabolomic one (fatty acids), the evolution of the antioxidant status, and the cytotoxic effect were determined comparatively for six months. This study presented for the first time that Aronia extract has a strong antimicrobial effect but also a presence of new organic acids that can be used as a biomarker. The functional supplement had the impact of a gradual increase in antioxidant status (DPPH scavenging activity) for up to three months and a subsequent decrease correlated with the reduction of the microbial load (especially for Enterobacteriaceae). The effect on metabolomic activity was specific, with butyric acid being generally unaffected (0.6–0.8 mg/mL) by the antimicrobial effect manifested after three months of administration. The pH was strongly acidic, corresponding to the constant presence of maximum values for acetic and lactic acid. The non-selective elimination of a part of the microbiota could also be correlated with a decrease in metabolomic efficiency. The results in the GIS1 system indicated for the first time that the controlled use of this extract had a pronounced antimicrobial and cytotoxic effect. This has helped to correct the dysbiotic pattern that results after the long-term use of sweeteners based on an increase of 0.2 log UFC/mL for favorable strains. Full article

Head and neck squamous cell carcinoma is highly aggressive type of cancer for which the available treatment often causes patients severe side effects. Eugenol (Eug) is the major active constituent of clove essential oil and is known to possess antitumor properties. The present study aimed to assess the in vitro cytotoxicity of eugenol in SCC-4, tongue squamous carcinoma cells, and also in HGF, human gingival fibroblasts. Both cell lines were treated with five concentrations of Eug (0.1–1 mM) for 72 h. Cellular viability was assessed, followed by cellular morphological evaluation and by staining of the nuclei and cytoskeleton. RT-PCR was conducted in order to find the effect eugenol had on the expression on Bad, Bax, and Bcl-2 genes. Eugenol induced a dose-dependent decrease in viability in both cell lines, with the SCC-4 cells being significantly more affected. HGF cells detached from the plate at the highest concentrations used, while SCC-4 cells changed their morphology in a dose-dependent manner, with rounding, floating cells, and confluency loss being observed. Apoptotic-like signs such as chromatin and actin filaments condensation were clearly seen in SCC-4 cells, while RT-PCR revealed a significantly increased expression of pro-apoptotic genes Bax and Bad. Therefore, eugenol exerts its cytotoxic effect in tongue squamous cell carcinoma through inducing apoptosis. Full article

Convolvulus arvensis is a medicinal plant in the family Convolvulaceae, which is used in traditional phytotherapy. The objective of this work was conducted to valorize essential oils of Convolvulus arvensis (EOCA) in terms of chemical composition, antioxidant, and antibacterial properties. To achieve this objective, the chemical composition was performed by the use of GC-SM. Antioxidant power was effectuated by the use of DPPH, FRAP, and TAC assays. Evaluation of the antimicrobial power was conducted against clinically important pathogenic bacteria (E. coli, K. pneumoniae, S. pneumoniae, and S. aureus) and fungi (A. niger, C. albicans, and A. flavus) by the use of disc diffusion and minimum inhibitory concentrations (MICs) assays. The results showed that the yield of recovered EOs from Convolvulus arvensis was 0.34% of the total mass of leaves and mainly was rich in cuprenne (34%), thymol (20%), himachalene (16%), and longifolene (10%). Notably, EOCA exhibited important antioxidant effects, wherein IC₅₀ (DPPH) and EC₅₀ (FRAP) were determined to be 30 µg/mL and 120 µg/mL, respectively, while the total antioxidant power was determined to be 508.0 ± 6.0 µg EAA/mg. An important antibacterial effect was noted for EOCA as an excellent inhibition zone was recorded against all bacterial strains, particularly K. pneumoniae and S. aureus with 14.27 ± 0.42 and 21.35 ± 0.76 mm, respectively. Similarly, MICs of K. pneumoniae and S. aureus were 21.35 ± 0.76 mm and 28.62 ± 1.65 µg/mL, respectively. Noticeably, important antifungal activity was shown by EOCA against all fungal strains wherein the inhibition zone diameters against all fungal species ranged from 19.44 ± 1.10 to 20.41 ± 1.81 mm. Notably, MICs of EOCA against F. oxysporum and C. albicans were 18.65 ± 0.94 and 19.38 ± 0.58 g/mL, respectively. The outcome of the present work showed that EOs from Convolvulus arvensis can be used to conceptualize drugs to manage diseases relative to free radicals and infections. Full article

Wogonin, one of the exceptional bioactive flavonoids found abundant in the roots of Huang-Qin (Scutellaria baicalensis Georgi), is a popular health-preserving Chinese medicine. The therapeutic applications can be expanded by improving its bioavailability. The 7-O-terpenylated wogonin consisting one to three prenyl units are chemically synthesized for increasing lipophilic nature for efficient uptake, and also an attempt in mimicry of naturally scarce terpenylated flavonoids found in limited plant families and bee propolis. Wogonin (W) and its lipophilic nature prenyl wogonin (W5), geranyl wogonin (W10), and farnesyl wogonin (W15) were comparatively studied with structure-relationship in immunotoxicity of cell livability on lymphoid, myeloid, and somatic origins cell lines. Anti-inflammatory functions characterized with nitric oxide inhibition and intracellular ROS level of LPS-activated murine macrophage RAW264.7 were assessed. Wogonin and its terpenylated derivatives have selectively influenced livability of lymphoid origin cells but not myeloid and somatic origin cells. The mitotic protein survivin gene expressions analysis further supported the selective suppressions on lymphoid origin YAC-1 cells by wogonin and geranyl wogonin, while oppositely boosted survivin expressions in LPS-activated macrophages. Moreover, wogonin exhibits dose-dependent inhibition on the nitric oxide (NO) production and iNOS gene expressions of LPS-activated RAW264.7 cells. Terpenylated wogonin exhibits profoundly superior control in intracellular ROS level and a sustained action with sound cell integrity than the wogonin. The enhanced cellular uptake with higher lipophilicity to membrane of 7-O-terpenylated wogonin may pose an important biological nature in facilitating better bioavailability and specific immunomodulatory actions of the category of terpenylated flavonoids. The 7-O-terpenylated wogonin having biological merit of fast membrane lipid bilayer integration, lower effective concentration, and better preserving immune cells functions and livability deserved further in-depth investigations and their broadly therapeutic applications. Full article

Bacterial virulence factors are mediating bacterial pathogenesis and infectivity. Collagenases are virulence factors secreted by several bacterial stains, such as Clostridium, Bacillus, Vibrio and Pseudomonas. These enzymes are among the most efficient degraders of collagen, playing a crucial role in host colonization. Thus, they are an important target for developing new anti-infective agents because of their pivotal roles in the infection process. A primary screening using a fluorescence resonance energy-transfer assay was used to experimentally evaluate the inhibitory activity of 77 compounds on collagenase A. Based on their inhibitory activity and chemical diversity, a small number of compounds was selected to determine the corresponding half maximal inhibitory con-centration (IC50). Additionally, we used molecular docking to get a better understanding of the enzyme–compound interaction. Several natural compounds (capsaicin, 4′,5-dihydroxyflavone, curcumin, dihydrorobinetin, palmatine chloride, biochanin A, 2′-hydroxychalcone, and juglone) were identified as promising candidates for further development into useful anti-infective agents against infections caused by multi-drug-resistant bacterial pathogens which include collagenase A in their enzymatic set. Full article

Berry volatiles are responsible for the berry aroma but there is limited information available on the health-promoting activities of berry volatiles. The objectives of this study were to evaluate the chemical composition of volatile extracts from black raspberries, blueberries, and blackberries and investigate their antiproliferative effect and apoptotic mechanisms on A549 lung cancer cells. The chemical composition of three berry volatile extracts (BVEs) was identified by using gas chromatography-mass spectrometry. Cells were treated with different dilutions of three BVEs for 48 h and determined for cell proliferation and apoptosis. Total volatiles in BVEs were 1.6–3.2 mg/L. Two-fold diluted BVEs significantly inhibited cell proliferation after 48 h, inducing apoptosis (p < 0.05). Blackberry volatile extract significantly reduced the inactive form of apoptotic proteins, including poly adenosine diphosphate-ribose polymerase (PARP), procaspase-9, and procaspase-3 compared to the control (p < 0.05). Blueberry volatile extract showed higher apoptotic cell death (p < 0.05) with a slightly higher cell population in G0/G1 phase than other berries. These results showed that volatile extracts from three berries have the antiproliferative effect on human lung adenocarcinoma cells partially via apoptosis, suggesting that volatiles from three berries may have potential anti-cancer activity through apoptosis in lung cancer. Full article

Oxidative stress and multiple erythrocyte abnormalities have been observed in hypertension. We focused on the effects of angiotensin-converting enzyme 2 (ACE2) inhibition by MLN-4760 inhibitor on angiotensin peptides, oxidative stress parameters, and selected erythrocyte quality markers in spontaneously hypertensive rats (SHR). We also investigated the potential effects of polyphenolic antioxidant taxifolin when applied in vivo and in vitro following its incubation with erythrocytes. SHRs were divided into four groups: control, taxifolin-treated, MLN-4760-treated, and MLN-4760 with taxifolin. MLN-4760 administration increased the blood pressure rise independent of taxifolin treatment, whereas taxifolin decreased it in control SHRs. Body weight gain was also higher in ACE2-inhibited animals and normalized after taxifolin treatment. However, taxifolin did not induce any change in angiotensin peptide concentrations nor a clear antioxidant effect. We documented an increase in Na,K-ATPase enzyme activity in erythrocyte membranes of ACE2-inhibited SHRs after taxifolin treatment. In conclusion, ACE2 inhibition deteriorated some selected RBC properties in SHRs. Although taxifolin treatment did not improve oxidative stress markers, our data confirmed the blood pressure-lowering potential, anti-obesogenic effect, and some “erythroprotective” effects of this compound in both control and ACE2-inhibited SHRs. In vitro investigations documenting different effects of taxifolin on erythrocyte properties from control and ACE2-inhibited SHRs accentuated the irreplaceability of in vivo studies. Full article

Harmine is a beta-carboline alkaloid present in various plants, including in the seeds of Peganum harmala L. This study aimed to investigate the anti-inflammatory activity and mechanism of harmine using macrophages stimulated with various toll-like receptor (TLR) agonists and a model of endotoxemia. The expression of inflammatory mediators induced by ligands of TLRs 2, 3, 4, and 9 were examined in thioglycollate-elicited peritoneal macrophages isolated from BALB/c and C57BL/6 mouse strains. Further, the activation of NF-κB, MAPK, AP-1, and STAT1 was explored using lipopolysaccharide (LPS) and polyinosinic:polycytidylic acid (poly(I:C)). Finally, the liver inflammatory response during endotoxemia was examined. Harmine inhibited inducible nitric oxide synthase, cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-12, and other markers induced by various TLR agonists. The inhibition of NF-κB activity by harmine occurred via the modulation of p65 phosphorylation, independent of IκBα degradation. The inhibition of AP-1 activity by harmine was associated with the modulation of JNK. Harmine inhibited the LPS-induced serine and tyrosine phosphorylation of STAT1, but only affected serine phosphorylation by poly(I:C) treatment. In vivo, harmine inhibited iNOS and COX-2 expression during endotoxemia. Collectively, the results show that harmine can be effective against infectious inflammation through modulation of NF-κB, JNK, and STAT1. Full article

Atractylodes lancea (Thunb.) DC. (AL) has been indicated in traditional prescriptions for the treatment of depression. However, the mechanism of action of AL in the treatment of depression is still unclear. This study aimed to investigate the antidepressant potential of AL using network pharmacology, molecular docking, and animal experiments. The active components of AL were retrieved from the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), and the depression-related targets were screened through the DisGeNET database. Overlapping targets of AL and depression were selected and analyzed. Ten active compounds of AL showed anti-depressant potential, including stigmasterol, 3β-acetoxyatractylone, wogonin, β-sitosterol, selina-4(14),7(11)-dien-8-one, atractylenolide I, atractylenolide II, atractylenolide III, patchoulene, and cyperene. These compounds target 28 potential antidepressant genes/proteins. Gene Ontology (GO) enrichment analysis revealed that the potential targets might directly influence neural cells and regulate neuroinflammation and neurotransmitter-related processes. The potential Kyoto Encyclopedia Genes and Genomes (KEGG) pathways for the antidepressant effects of AL include neuroactive ligand–receptor interactions, calcium signaling pathways, dopaminergic synapse, interleukin (IL)-17 signaling pathways, and the pathways of neurodegeneration. IL-6, nitric oxide synthase 3 (NOS), solute carrier family 6 member 4 (SLC6A4), estrogen receptor (ESR1), and tumor necrosis factor (TNF) were the most important proteins in the protein–protein interaction network and these proteins showed high binding affinities with the corresponding AL compounds. AL showed an antidepressant effect in mice by decreasing immobility time in the tail suspension test and increasing the total contact number in the social interaction test. This study demonstrated the antidepressant potential of AL, which provides evidence for pursuing further studies to develop a novel antidepressant. Full article

(1) Background: Osteoporosis is a disease in which bones are weakened and fractured easily because of various factors. It is mainly observed in elderly and postmenopausal women, and it continues to carry high economic costs in aging societies. Normal bone maintains a healthy state through a balanced process of osteoclast suppression and osteoblast activation; (2) Methods: In this study, osteoclast inhibition was induced by inhibiting osteoclast differentiation using ginseng protopanaxadiol-enriched rice (PPD-rice) seed extract. To analyze the effect of PPD-rice extract on the inhibition of osteoclast differentiation, bone marrow macrophages extracted from mice were treated with PPD-rice and Dongjin seed (non-transformed rice) extracts and analyzed for the inhibition of osteoclast differentiation; (3) Results: The results illustrated that PPD-rice extract reduced the transcription and translation of NFATc1, a modulator of osteoclast formation, decreased the mRNA expression of various osteoclast differentiation marker genes, and reduced osteoclast activity. Moreover, the bone resorptive activity of osteoclasts was diminished by PPD-rice extract on Osteo Assay plates; (4) Conclusions: Based on these results, PPD-rice extract is a useful candidate therapeutic agent for suppressing osteoclasts, an important component of osteoporosis, and it could be used as an ingredient in health supplements. Full article

Betulinic acid, a small molecule from pentacyclic triterpenes class, has been widely studied for its antitumor activity, revealing that it induces the apoptosis of tumor cells in a selective manner. In recent years, digoxin, a cardiac glycoside found particularly in the plant species Digitalis lanata, has drawn interest for its potential antitumor properties. The present study was designed to evaluate the antimelanoma potential of betulinic acid (BA), digoxin (DG), and their association (DG + BA). In vitro assessments were performed 24 h post-treatment on two human melanoma cell lines (SK-Mel-28 and RPMI-7951). In addition, the potential irritant effects of the test samples were evaluated using the chorioallantoic membrane of hen’s eggs. BA and DG exhibit a concentration-dependent cytotoxic activity, with the combination of the two having a more marked effect on the decrease in cell viability (~17% for SK-Mel-28 cells and ~23% for RPMI-7951 cells). Further, morphological changes (rounding of the cells and their separation from the plaque) and alterations in the nucleus and actin fibers (condensation of chromatin and actin fibers, formation of apoptotic bodies) were observed, indicating an apoptotic-like process. Moreover, no irritating effects were observed in ovo. As a result, DG + BA acid may have synergistic potential in the antitumor treatment of melanoma, but future studies are needed in order to clarify the biological mechanisms involved. Full article

Atranorin (ATR) is one of lichens’ many known secondary metabolites. Most current studies have investigated the various effects of ATR in vitro and only sporadically in vivo. The latest data indicate that ATR may have anxiolytic/antidepressive effects. This study aimed to analyze the potential of ATR in a depression-like state in male Wistar rats. Pregnant females were stressed by restricting their mobility in the final week of pregnancy three times a day for 45 min each, for three following days. After birth, progeny aged 60 days was stressed repeatedly. The male progeny was divided into three groups as follows: CTR group as a healthy control (n = 10), DEP group as a progeny of restricted mothers (n = 10), and ATR group as a progeny of restricted mothers, treated daily for one month with ATR (n = 10; 10 mg/kg of body weight, p.o.). Our results show that ATR acts as an antioxidant and markedly changes animal behavior. Concomitantly, hippocampal neurogenesis increases in the hilus and subgranular zone, together with the number of NeuN mature neurons in the hilus and CA1 regions. Our results indicate a potential antidepressant/anxiolytic effect of ATR. However, further studies in this area are needed. Full article

Based on the vernacular reputation of Coriandrum sativum and Citrus limon to treat hypertension, this study was designed to explore the cardiovascular effects of C. sativum (CS) and C. limon (CL) on arsenic-induced hypertension and endothelial damage. Hypertension was induced by arsenic (100 ppm) in drinking water. The crude methanolic extracts of CS and CL were tested for in vivo and in vitro activities using Power Lab. High performance liquid chromatography analysis of CS and CL showed the presence of phenolic compounds. In anesthetized rats, CS (50 mg) and CL (10 mg) showed a marked decrease in blood pressure of 51% and 35%, respectively. Similarly, ascorbic acid (10 mg) also showed a decreased blood pressure (41%). The CS and CL caused complete relaxation (0.003–5 mg/mL) against phenylephrine (1µM) and high K⁺ (80 mM)-induced contraction. The CS and CL, independently and in combination, exhibited marked (p < 0.001) attenuation in the blood pressure of the arsenic-induced hypertensive rats when compared with the controls. The beneficial effects of the CS and CL were also observed on lipid peroxidation and eNOS. These data suggest that CS and CL possess significant antihypertensive activity, possibly mediated via endothelium protection, and anti-oxidant effects. Thus, this study provides a rationale for the medicinal use of CS and CL in hypertension and also against arsenic-induced cardiovascular complications. Full article

Glycyrrhiza glabra or licorice has long been known as a commonly used Ayurvedic herb. This study aims to investigate the effect of extraction methods on the chemical composition and biologically active properties of Glycyrrhiza glabra extract samples. The highest yield of the Glycyrrhiza glabra extract (21.31 ± 0.64 wt.%) was produced using the Soxhlet extraction method with methanol. The highest concentrations of biologically active substances (3,4-dihydroxybenzoic acid, n-coumaric acid, luteolin-7-glucoside, acacetin, apigenin-7-O-glucoside, chicoric acid, and hesperetin) were found in these samples of Glycyrrhiza glabra extracts. When applying the maceration method using a mixture of solvents methanol-NaOH, rosmarinic acid was identified, and catechin was found in large quantities with a mixture of methanol-trifluoroacetic acid (TFA). Growth inhibition zones were determined for Escherichia coli (13.6 ± 0.41 mm), Pseudomonas aeruginosa (10.8 ± 0.32 mm), Bacillus subtilis (16.1 ± 0.48 mm), and Candida albicans (13.2 ± 0.39 mm) when exposed to samples of Glycyrrhiza glabra extracts obtained by the Soxhlet method with methanol. The antioxidant activity of Glycyrrhiza glabra extract samples obtained by the Soxhlet method was 117.62 ± 7.91 µmol Trolox equivalent/g, using the ABTS method (highest value), and 23.91 ± 1.12 µmol Trolox equivalent/g according to the FRAP method (smallest). The antioxidant activity of the extract samples according to the DPPH method was an intermediate value of 58.16 ± 3.90 µmol Trolox equivalent/g. Antibacterial and antioxidant activities are manifested by the polyphenolic compounds and flavonoids contained in the samples of the methanol extract of Glycyrrhiza glabra produced using the Soxhlet method. These Glycyrrhiza glabra extract samples have the potential to become a natural alternative to existing therapies for the elimination of bacterial infections or the prevention of premature aging caused by free radicals and oxidative stress in the human body. Full article

The emergence of resistance to pancreatic cancer (PC) current treatment requires the development of new therapeutic strategies. In this context, bioactive molecules from plant extracts have shown excellent properties to improve classical therapy against this type of tumor. This systematic review aims to collect all the in vitro studies related to the antiproliferative activity of isolated plant molecules that support their applicability in PC. A total of 620 articles published in the last 10 years were identified, although only 28 were finally included to meet the inclusion criteria. Our results reflect the most important biomolecules from natural compounds that induce cell death in PC and their essential mechanism of cell death, including apoptosis, pathways activated by the KRAS mutation and cycle cell arrest, among others. These in vitro studies provide an excellent molecule guide showing applications against PC and that should be tested in vivo and in clinical trials to determine their usefulness to reduce PC incidence and to improve the prognosis of these patients. However, natural compounds are isolated in small amounts, which prevents comprehensive drug screening, being necessary the role of organic synthesis for the total synthesis of natural compounds or for the synthesis of their simplified and bioactive analogs. Full article

Metabolic dysfunctions linked to obesity carry the risk of co-morbidities such as diabetes, hepatorenal, and cardiovascular diseases. Coumarins are believed to display several biological effects on diverse adverse health conditions. This study was conducted to uncover the impact of cichoriin on high-fat diet (HFD)-induced obese rats. Methods: Obesity was induced in twenty rats by exposure to an HFD for six weeks. The rats were randomly divided into five groups; group I comprised five healthy rats and was considered the control one. On the other hand, the HFD-induced rats were divided into the following (five per each group): group II (the HFD group), groups III (cichoriin 50 mg/kg) and IV (cichoriin 100 mg/kg) as the treatment groups, and group V received atorvastatin (10 mg/kg) (as a standard). Triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), alanine transaminase (ALT), aspartate transaminase (AST), creatine kinase MB (CK-MB), urea, creatinine, the hepatic and renal malondialdehyde (MDA) as well as reduced glutathione (GSH) levels were assessed. Histopathological analysis of the heart, kidney, and liver tissues was investigated. mRNA and protein expressions of the peroxisome proliferator-activated receptor gamma (PPAR-γ) were estimated. Results: The administration of cichoriin alleviated HFD-induced metabolic dysfunctions and improved the histopathological characteristics of the heart, kidney, and liver. Additionally, the treatment improved the lipid profile and hepatic and renal functions, as well as the oxidative balance state. Cichoriin demonstrated an upregulation of the mRNA and protein expressions of PPAR-γ. Taken together, these findings are the first report on the beneficial role of cichoriin in alleviating adverse metabolic effects in HFD-induced obesity and adapting it into an innovative obesity management strategy. Full article

Soy isoflavones possess antioxidative, anti-inflammatory, anti-diabetic and phytoestrogenic properties. Soybean residue contains a fair amount of nutrients such as glycosylated isoflavones, minerals and dietary fibers, and is a substantial waste product produced from soymilk and tofu manufacturing. A solid-state fermentation of soybean residue by Rhizopus oligosporus or co-inoculated with Lactiplantibacillus plantarum improves the availability of isoflavones and GABA content which is attributed to ameliorated hyperglycemic symptoms in STZ-induced hyperglycemic mice. The effortless solid-state fermentation with present microbial manipulation supports an anti-hyperglycemia value-added application of soybean residue for functional food development. Background: Due to an awareness of the food crisis and with a rapidly rising prevalence of diabetes, recycling the substantial fibrous soybean residue disposed from soy industries has received consideration. Methods: Lactiplantibacillus plantarum was previously screened for active glutamate decarboxylase, and β-glucosidase activities were adopted for the fermenting of soybean residue using a traditional tempeh solid-state fermenting process with fungal Rhizopus oligosporus. Fermented soybean residue was chemically analyzed and functionally assessed in in vitro and in vivo hyperglycemic conditions. Results: A 48 h longer solid-state fermentation of the soybean residue co-inoculated with R. oligosporus and L. plantarum showed improved contents of isoflavone aglycones and GABA which were attributed to augmented antioxidative capacity, lowered ROS level, improved blood biochemistry, and better blood glucose homeostasis in STZ-induced hyperglycemic mice. Conclusion: The advantages of a food industrial effortless fermentation process, and a health nutritional endorsing anti-hyperglycemic value-added property offer a practical alternative in recycled soybean residue. Full article

The objective of this study was to characterize the bioactive ingredients and antiulcer effects of Lactuca sativa leaves. Several bioactive chemicals were found in the cold methanolic extract of Lactuca sativa leaves after gas chromatography-mass spectrometry (GC-MS) research: 9,12-octadecadienoic acid (Z,Z)-, cyclononasiloxane, octadecamethyl-, n-hexadecanoic acid, Hexadecanoic acid, 2-hydroxy-1-(hydroxymethyl)ethyl, octadecanoic acid, 2-hydroxy-1-(hydroxymethyl)ethyl ester, 9-octadecenamide, (Z)-, hexadecanoic acid, stigmasterol, benzothiazole, ethyl iso-allocholate, and octacosane. Distinct fingerprint regions in GCMS indicated the existence of bioactive compounds. The leaf powder of Lactuca sativa (LPL) demonstrated substantial antiulcer properties at 400 mg/kg, which was almost equivalent to the standard drug at 20 mg/kg. The cytokine network was efficiently regulated by reducing the production of proinflammatory cytokines such as IL-1β, IL-6, and TNF-α. The levels of caspase-3 and caspase-9 were also considerably lowered at p < 0.05 significant level. Full article

Teucrium polium L. is commonly used in folk medicine to treat hypertension and diabetes and to heal wounds. The present work aimed to evaluate the different biological activities of T. polium hydroalcoholic extract, its total phenol and flavonoid content, and its mineral elements. Results showed that T. polium extract showed significant antioxidant potential in 2-diphenyl-1-picrylhydrazyl (DPPH) assay with IC₅₀ equal to 8.68 μg/mL but with moderate activity in galvinoxyl assay with IC₅₀ of 21.82 μg/mL and mild activity in the β-carotene assay. It also showed a pronounced anti-hyperglycemic activity using α-amylase inhibitory assay (IC₅₀ = 111.68 µg/mL) and exceeds that of acarbose. T. polium showed excellent activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC₅₀ values of 28.69 and 4.93 μg/mL, respectively, postulating its promising anti-Alzheimer potential. The plant extract exhibited a strong anti-inflammatory effect with Bovine Serum Albumin (BSA) denaturation inhibitory potential estimated by 97.53% at 2 mg/mL, which was further confirmed by the in vivo carrageen-induced edema model. The extract revealed its richness in flavonoids and phenols, evidenced by its polyphenols content (36.35 ± 0.294 μg GAE/mg) and flavonoids (24.30 ± 0.44 μg QE/mg). It is rich in minerals necessary for human health, such as calcium, potassium, iron, sodium, magnesium, manganese and zinc. Molecular docking performed for previously identified compounds on human α-amylase, 5-lipoxygenase (5-LOX) and acetylcholine esterase confirmed the results. Thus, it can be concluded that T. polium can be a good candidate for alleviating many health-debilitating problems and can be highly beneficial in the pharmaceutical industry and medical research. Full article

Herbal extracts are part of the solution to the increased demand for organic health care products. Traditionally, the different extracts prepared from Haplophyllum tuberculatum (Forsskal) A. Juss (H. tuberculatum) have been widely used to treat a wide range of illnesses. The aim of this study is to evaluate the antioxidant, analgesic, anti-inflammatory, and wound healing potential of the aqueous (HTAE) and ethanolic (HTEE) extracts of this plant as well as identify its major phytochemical components using LC-MS. Phytochemical analysis of both extracts revealed a rich composition and especially high amounts of glycosylic flavonols, 65.37% and 68.77% for the HTEE and HTAE, respectively. The antioxidant assays performed (DPPH, FRAP and TAC) indicated the excellent activity of the ethanolic extract while the in vivo activities (analgesic, anti-inflammatory, and healing potential) indicated the excellent activity of the aqueous extract. These findings support the therapeutic use of this plant by preventing pain and inflammation and promoting wound healing. To uncover, identify, and isolate compounds of potential medicinal and therapeutic significance, more studies on this species are required. Full article

Saussurea hypoleuca belongs to the family Asteraceae, which has previously shown hepatoprotective, anticancer, and antioxidant activity. This study aimed to evaluate the antihyperglycemic and antihyperlipidemic activity of its root methanol extract and various fractions for the first time. This was performed using alloxan-induced diabetes in the rat model for both short, and long-term periods using different administration doses. Different biochemical parameters were studied and further consolidated by histopathological examination and in silico molecular modeling. The results showed that in the long-term study, at a dose of 400 mg/kg b.wt, the ethyl acetate fraction caused a pronounced reduction in fasting blood glucose level (FBG) and glycated hemoglobin (HbA_1c) by 77.2% and 36.8%, respectively, compared to the diabetic group. This was confirmed by the histopathological examination of the animals’ pancreatic sections. The ethyl acetate fraction also showed a reduction in total cholesterol (TC), total glycerides (TG), and low-density lipoprotein cholesterol (LDL-C) levels. It improved kidney and liver functions, causing a reduction in aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine transaminase (ALT), urea, and creatinine levels. This is mainly attributed to its richness in secondary metabolites. Molecular docking showed that all the tested compounds showed certain inhibitory potential towards human α-glucosidase (HAG) and ATP citrate lyase (ACL). Thus, Saussurea hypoleuca roots can help in the management of hyperglycemia, hyperlipidemia, and hepatic and kidney dysfunction. Full article

In cancer management, drug resistance remains a challenge that reduces the effectiveness of chemotherapy. Several studies have shown that curcumin resensitizes cancer cells to chemotherapeutic drugs to overcome resistance. In the present study, we investigate the potential therapeutic role of curcumin in regulating the proliferation of drug-resistant cancers. Six drug-sensitive (MCF7, HCT116, and A549) and -resistant (MCF7/TH, HCT116R, and A549/ADR) cancer cell lines were treated with curcumin followed by an analysis of cytotoxicity, LDH enzyme, total reactive oxygen species, antioxidant enzymes (SOD and CAT), fibrosis markers (TGF-β1 protein, fibronectin, and hydroxyproline), and expression of cellular apoptotic markers (Bcl-2, Bax, Bax/Bcl-2 ratio, Annexin V, cytochrome c, and caspase-8). Additionally, the expression of cellular SIRT1 was estimated by ELISA and RT-PCR analysis. Curcumin treatment at doses of 2.7–54.3 µM significantly reduced the growth of sensitive and resistant cells as supported with decreased viability and increased cellular LDH enzyme of treated cells compared to controls non-treated cells. Curcumin also at doses of 2.7 and 54.3 µM regulated the fibrogenesis by reducing the expression of fibrotic markers in treated cells. Analysis of apoptotic markers indicated increased Bax, Bax, Bax/Bcl-2 ratio, Annexin V, caspase-8, and cytochrome c expression, while Bcl-2 expressions were significantly reduced. In curcumin-treated cells at 2.7 μM, non-significant change in ROS with significant increase in SOD and CAT activity was observed, whereas an increase in ROS with a reduction in respective antioxidant enzymes were seen at higher concentrations along with significant upregulation of SIRT1. In conclusion, the present study shows that curcumin induces anticancer activity against resistant cancer cell lines in a concentration- and time-dependent manner. The protective activities of curcumin against the growth of cancer cells are mediated by modulating oxidative stress, regulating fibrosis, SIRT1 activation, and inducing cellular apoptosis. Therefore, curcumin could be tested as an auxiliary therapeutic agent to improve the prognosis in patients with resistant cancers. Full article

Background: Recently, crop byproducts are considered a hot topic and can be converted into beneficial products. Cauliflower is well-known for its protective effects against oxidative stress-induced damage. The current study aimed to investigate the chemical profile and the ameliorative effects of cauliflower leaf extract (CL) on gentamicin-induced renal and hepatic injuries in rats. Methods: Cauliflower leaf was extracted with methanol to give the total methanol extract (TME) followed by the determination of total phenolic contents (TPC). Rats were divided into five groups; Group I was assigned as the control group, while the other groups were injected with gentamicin for ten days. Group II was given distilled water. Rats in groups III and IV were treated with oral CL (200 mg/kg and 400 mg/kg, respectively). Group V received L-cysteine (as a positive control). The functions of the kidneys and liver; oxidative stress and morphological and apoptotic changes of renal and hepatic tissues were assessed. Results: The TME was subjected to chromatographic techniques to yield ferulic acid, vanillic acid, p-coumaric acid and quercetin. TPC was 72.31 mg GAE/g of dried extract. CL treatment dose-dependently ameliorated gentamicin-induced impaired kidney and liver functions and improved the histopathological appearance of both organs. It also reduced gentamicin-induced oxidative stress. CL demonstrated downregulation of mRNA and protein expressions of IL-1β and NF-κB compared to nontreated rats. In silico interaction of the isolated compounds with amino acid residues of IL-1β and NF-κB might explain the current findings. Conclusion: Taken together, this study raises the waste-to-wealth potential of cauliflower to mitigate gentamicin-induced hepatorenal injury and convert the waste agromaterials into valuable products. Full article

Approximately 1 in 20 people develops kidney stones at some point in their life. Although the surgical removal of stones is common, the recurrence rate remains high and it is therefore important to prevent the occurrence of kidney stones. We chose Astragalus membranaceus (AM), which is a traditional Chinese medicine, to study the prevention of urolithiasis using a Drosophila model based on our previous screening of traditional Chinese herbs. Wild-type Drosophila melanogaster Canton-S adult fruit flies were used in this study. Ethylene glycol (EG, 0.5%) was added to food as a lithogenic agent. The positive control agent (2% potassium citrate (K-citrate)) was then compared with AM (2, 8, and 16 mg/mL). After 21 days, the fruit flies were sacrificed under carbon dioxide narcotization, and the Malpighian tubules were dissected, removed, and processed for polarized light microscopy examination to observe calcium oxalate (CaOx) crystallization. Then, the ex vivo dissolution of crystals in the Malpighian tubules was compared between K-citrate and AM. Survival analysis of the EG, K-citrate, and AM groups was also performed. Both 2% K-citrate and AM (16 mg/mL) significantly inhibited EG-induced CaOx crystal formation. Mean lifespan was significantly reduced by the administration of EG, and the results were significantly reversed in the AM (8 and 16 mg/mL) groups. However, AM extract did not directly dissolve CaOx crystals in Drosophila Malpighian tubules ex vivo. In conclusion, AM extract decreased the ratio of CaOx crystallization in the Malpighian tubules and significantly ameliorated EG-induced reduction of lifespan. AM prevented CaOx crystal formation in the Drosophila model. Full article

Enhancement of glycolysis and glutaminolysis are the two most common modalities associated with metabolic reprogramming in rheumatoid arthritis (RA). This enhancement is concomitant to the upregulation of hexokinase 2 (HK2) and glutaminase 1 (GLS1). Hence, the current study was undertaken to identify potential phytobiological inhibitors against HK2 and GLS1, from Dracaena (Sansevieria) trifasciata, an indigenous ethnomedicinal plant found in Pakistan, using computational analysis. Phytobiologics from Dracaena trifasciata were assessed for their ability to co-inhibit HK2 and GLS1 via molecular docking and molecular dynamics simulations. The results underscored seven phytobiologics with promising binding affinities for both HK2 and GLS1. Molecular dynamics simulations further elucidated that all seven identified phytobiologics inhibited HK2 by forming stable complexes but only five amongst the seven had the potential to form stable complexes with GLS1 in real time, thereby implying the potential of co-inhibition for these five compounds. Compound 28MS exhibited an equally strong binding profile for both HK2 (−8.19 kcal/mol) and GLS1 (−8.99 kcal/mol). Furthermore, it exhibited a similar trend in stability during simulation for both targets. Our results serve as a primer for a more lucid understanding towards co-inhibition of HK2 and GLS1 using multiple computational approaches. The identified phytobiologics should undergo in-vitro and in-vivo validation to corroborate their therapeutic potential in RA. Full article

The plant Saussurea costus (Falc) Lipsch has many biological activities and a strong curative and preventive power against a variety of diseases including cancer, diabetes, and hemorrhoids. In the current study, phytochemical screening was carried out as well as an investigation of the antilithiatic and antioxidant activities of aqueous and ethanolic extracts of this plant. The results showed that aqueous and ethanolic extracts were effective in reducing cystine stone mass and that the aqueous extract of Saussurea costus (Falc) Lipsch had the highest percentage of dissolution (6.756 ± 1.024) (p < 0.05). A turbidimetric method and a crystallization test were used to evaluate the antilithiatic activity of an aqueous and ethanolic extract of this plant on calcium oxalate crystallization. The results of these methods revealed that the ethanolic extract of this plant has a significant inhibitory effect on calcium oxalate crystallization, with a percentage inhibition of (91.017 ± 0.299) (p < 0.05) for a concentration of 2 mg mL⁻¹. The DPPH method revealed that the ethanolic extract of Saussurea costus (Falc) Lipsch with a concentration of (IC50 = 0.12325 mg mL⁻¹) had the highest IC50, whereas the FRAP method revealed that the aqueous extract of Saussurea costus (Falc) Lipsch with a concentration of 300 µg mL⁻¹ has the most significant reducing power with (OD = 0.56 ± 0.05). These findings indicate that aqueous and ethanolic extracts of Saussurea costus (Falc) Lipsch had a significant effect on whewellite and weddellite and a greater free radical scavenging effect but had no effect on cystine dissolution. Full article

Since osteoporosis critically influences the lives of patients with a high incidence, effective therapeutic treatments are important. Quercetin has been well recognized as a bone-sparing agent and thus the underlying mechanisms warrant further investigation. In the current study, the network pharmacology strategy and zebrafish model were utilized to explain the potential pharmacological effects of quercetin on osteoporosis. The potential targets and related signaling pathways were explored through overlapping target prediction, protein–protein interaction network construction, and functional enrichment analysis. Furthermore, we performed docking studies to verify the specific interactions between quercetin and crucial targets. Consequently, 55 targets were related to osteoporosis disease among the 159 targets of quercetin obtained by three database sources. Thirty hub targets were filtered through the cytoNCA plugin. Additionally, the Gene Ontology functions in the top 10 respective biological processes, molecular functions, and cell components as well as the top 20 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were depicted. The most significance difference in the KEGG pathways was the TNF signaling pathway, consisting of the Nuclear Factor Kappa B Subunit (NF-κB), Extracellular Regulated Protein Kinases (ERK) 1/2, Activator Protein 1 (AP-1), Interleukin 6 (IL6), Transcription factor AP-1 (Jun), and Phosphatidylinositol 3 Kinase (PI3K), which were probably involved in the pharmacological effects. Moreover, molecular docking studies revealed that the top three entries were Interleukin 1 Beta (IL1B), the Nuclear Factor NF-Kappa-B p65 Subunit (RelA), and the Nuclear Factor Kappa B Subunit 1 (NFKB1), respectively. Finally, these results were verified by alizarin red-stained mineralized bone in zebrafish and related qPCR experiments. The findings probably facilitate the mechanism elucidation related to quercetin anti-osteoporosis action. Full article

Ecdysteroids represent arthropods’ steroidal hormones, and they exist in about 5–6% of plant species. In this study, the enzyme inhibitory activity of 20 ecdysteroids was assessed for the first time via determining their inhibition versus acetylcholinesterase, butyrylcholinesterase, tyrosinase, as well as α-amylase enzymes. Furthermore, 20-Hydroxyecdysone-2,3,22-tri-O-acetate (4) showed the highest inhibition of acetylcholinesterase and butyrylcholinesterase with values of 5.56 and 4.76 mg GALAE/g, respectively. All ecdysteroids displayed tyrosinase inhibitory effects, whereas the most potent was viticosterone E (7) with 78.88 mg KAE/g. Most ecdysteroids had similar amylase inhibitory properties; meanwhile, the best α-amylase inhibitory potential was observed with viticosterone E-diacetonide (18) (0.35 mmol ACAE/g). Most of the tested compounds showed tyrosinase inhibitory potential; therefore, they were exposed to molecular docking evaluation using the tyrosinase enzyme. Viticosterone E (7) showed the best ranking score with a docking score of −5.716 Kcal/mol and made three separate H-bonds with Gly281, Asn81, and His85. From ADMET /TOPKAT in silico evaluation, it was obvious that most of the compounds displayed reasonable pharmacodynamic and pharmacokinetic properties; however, their toxicity should be carefully monitored by adjusting their doses while investigating their activity after incorporation into dosage forms. Principal component analysis (PCA) based upon the in vitro and in silico data was carried out to visualize the differences between the tested compounds better. PCA score plot successfully classifies the compounds into four main clusters that, in turn, reflects the similarities and differences among the clustered compounds with respect to their biological, pharmacokinetic, and pharmacodynamic properties that are mainly influenced by the similarity in the chemical structure. Thus, ecdysteroids can act as effective drug entities for alleviating several disorders owing to their enzyme inhibitory potential. Full article

This study aims to see if Ginseng^® can reduce the hepatorenal damage caused by malathion. Four groups of forty male Wistar albino rats were alienated. Group 1 was a control group that got orally supplied corn oil (vehicle). Group 2 was intoxicated by malathion dissolved in corn oil orally at 135 mg/kg/day. Group 3 orally received both malathion + Panax Ginseng^® (300 mg/kg/day). Group 4 was orally given Panax Ginseng^® at a 300 mg/kg/day dose. Treatments were administered daily and continued for up to 30 consecutive days. Malathion’s toxic effect on both hepatic and renal tissues was revealed by a considerable loss in body weight and biochemically by a marked increase in liver enzymes, LDH, ACP, cholesterol, and functional renal markers with a marked decrease in serum TP, albumin, and TG levels with decreased AchE and Paraoxonase activity. Additionally, malondialdehydes, nitric oxide (nitrite), 8-hydroxy-2-deoxyguanosine, and TNFα with a significant drop in the antioxidant activities were reported in the malathion group. Malathion upregulated the inflammatory cytokines and apoptotic genes, while Nrf2, Bcl2, and HO-1 were downregulated. Ginseng^® and malathion co-treatment reduced malathion’s harmful effects by restoring metabolic indicators, enhancing antioxidant pursuit, lowering the inflammatory reaction, and alleviating pathological alterations. So, Ginseng^® may have protective effects against hepatic and renal malathion-induced toxicity on biochemical, antioxidant, molecular, and cell levels. Full article

Osthole (OS) is a natural coumarin with a long history of medicinal use in a variety of diseases, such as itch and menstrual disorders. In recent years, OS has been shown to treat inflammation and reduce the expression and activity of NF-κB, although its mechanism of action is still unclear. Overexpression of inflammatory cytokines can have many negative effects in the body, including inducing preterm labor; thus, the modulation of inflammation by OS and its derivatives may be able to delay preterm birth, increasing neonatal survival rates. The objectives of this study were to screen and identify the derivatives of OS with the highest potential for binding capacity to inflammatory mediators NF-κB, TNF-α, and ERK1, and to measure the drug-like properties of these compounds. GLIDE docking in Schrodinger Maestro software was used to calculate docking scores for a variety of semi-synthetic OS derivatives against three proteins involved in inflammation: NF-κB, TNF-α, and ERK1. Schrodinger Qikprop was also used to measure the pharmaceutically relevant properties of the compounds. The protonated demethoxy osthole 1 showed the highest docking of all the proteins tested, while the deprotonated demethoxy osthole 2 consistently had the lowest scores, denoting the importance of pH in the binding activity of this derivative. The lowest docking was at NF-κB, suggesting that this is less likely to be the primary target of OS. All of the screened derivatives showed high drug potential, based on their Qikprop properties. OS and its derivatives showed potential to bind to multiple proteins that regulate the inflammatory response and are prospective candidates for delaying preterm birth. Full article

Malathion (MAL) is an insecticide that has been linked to reproductive system damage in both humans and animals. In the present investigation, the antitoxic effects of coffee and olive oils on MAL-induced testicular dysfunctions were evaluated. MAL-intoxicated rats were supplemented with coffee and olive oils (400 mg/kg) for 7 weeks. Exposure to MAL resulted in statistically altered antioxidant enzymes and histopathological findings of necrotic seminiferous tubules and spermatogenetic arrest in rats after seven weeks of treatment. The effects of MAL intoxication on physiological and histopathological changes were improved by the use of these oils. Murine double minute 2 (MDM2) was found to interact well with chlorogenic acid and oleuropein, two compounds from coffee and olive oils, respectively. Coffee oil and olive oil were found to be promising therapeutic agents for MAL-induced testicular toxicity and oxidative damage. Full article

Alzheimer’s disease (AD), the most common dementia worldwide, remains without an effective treatment to this day despite intensive research conducted during the last decades. In this context, researchers have turned their attention towards the prevention of this pathology, focusing on early detection and better control of the most important risk factors, concomitantly with trying to find potentially protective factors that may delay the onset of AD. From the multitude of factors studied, coffee (especially its main component, caffeine) is a current interesting research topic, taking into consideration the contradictory results of recent years’ studies. On the one hand, much of the evidence from fundamental research suggests the potentially protective trait of caffeine in AD, while other data mainly from human studies lean toward no correlation or even suggesting that caffeine is a veritable risk factor for dementia. Given the methodological heterogeneity of the studies, this review aims to bring new evidence regarding this topic and to try to clearly establish a correlation between the two entities. Thus, in the first part, the authors make a clear distinction between the effects of coffee and the effects of caffeine in AD, presenting a rich basis of clinical trials on both animal models and the human subject. Subsequently, the main pathophysiological mechanisms that would explain the action of caffeine in the etiopathogenesis of AD are reviewed. Finally, the role of computational models is presented, having beneficial impact on both better understanding of the disease mechanism and the development of new therapeutic approaches for AD prevention. Full article

Lavender aqueous extracts are widely used in the Moroccan traditional medicine for their antibacterial properties. However, previous research have generally focused on investigating the antibacterial activity of lavender essential oils. The aim of this study is to evaluate the antibacterial activity of the Moroccan Lavandula pedunculata (Mill.) Cav. aqueous extract, alone, as well as in combination with extracts of other plant species known for their antibacterial activity: Salvia rosmarinus Spenn., Salvia lavandulifolia Vahl. and Origanum compactum Benth. We have tested the antibacterial activity of L. pedunculata, S. rosmarinus, S. lavandulifolia and O. compactum aqueous extracts individually and in combination against 34 strains using the agar dilution method. The combination effect was evaluated using the fractional inhibitory concentration (FIC). Polyphenol and tannin contents were determined using Folin-Ciocalteu reagent, and then some phenolic compounds were identified using UHPLC-MS. All the extracts displayed a large spectrum of antibacterial activity, especially against staphylococci, streptococci, Mycobacterium smegmatis and Proteus mirabilis. The minimum inhibitory concentration (MIC) values reached 0.15 ± 0.00 mg/mL for Staphylococcus warneri tested with S. lavandulifolia and 0.20 ± 0.07 mg/mL for Staphylococcus epidermidis tested with L. pedunculata or S. rosmarinus. Association of the L. pedunculata extract with S. rosmarinus, S. lavandulifolia and O. compactum showed synergistic effects (FIC ≤ 1). Moreover, the association of L. pedunculata with S. lavandulifolia was active against most of the Gram-negative strains resistant to the individual extracts. Determination of polyphenol and tannin contents showed the richness of the studied plants in these compounds. Additionally, chromatographic analysis demonstrated the high presence of rosmarinic acid in all the studied plant extracts. To our knowledge, this is the first study that shows the enhancing effect of the antibacterial activity of L. pedunculata aqueous extract combined with S. rosmarinus, S. lavandulifolia and O. compactum. These results confirm the effectiveness of the plant mixtures commonly used by traditional healers in Morocco and suggest that L. pedunculata might be used as an antibacterial agent either alone or, more efficiently, in combination with S. rosmarinus, S. lavandulifolia and O. compactum. Full article

A novel coronavirus (COVID-19) was identified as one of the severe acute respiratory syndrome coronaviruses (SARS-CoV-2) and emerged as a pandemic in 2020. Thus, there is an urgent need to screen and develop an agent to suppress the proliferation of viral particles of SARS-CoV-2, and several drugs have entered clinical trial phases to assess their therapeutic potential. The objective of the present study is to screen phytochemicals against the main viral protease using molecular docking studies. The phytochemicals vasicine, vasicinone, vasicinolone, vasicol, vasicolinone, adhatodine, adhavasicinone, aniflorine, anisotine, vasnetine, and orientin from Adhatoda vasica were selected, and the compounds were docked with various viral protein targets, including specific SARS-CoV-2 main protease (PDBID:6Y84), using AutoDock, Schrodinger, Biovia discovery studio, and virtual screening tools. Adhatodine and vasnetine showed a better binding affinity of −9.60 KJ/mol and −8.78 KJ/mol, respectively. In molecular docking simulations for 10 ns, these compounds illustrated strong hydrogen-bonding interactions with the protein active site and induced a potential conformational change in the ligand-binding site. The results were compared with the antiviral drugs nirmatrelvir and ritonavir. These results suggest that these phytochemicals can be studied as potential inhibitors against SARS-CoV-2 protease and may have an antiviral effect on coronavirus. However, further in vitro and in vivo efficacy activity needs to be investigated for these phytochemicals. Full article

This study aims to examine the ability of apple vinegar on phenylhydrazine (PHZ)-induced hemolytic anemia in Wistar rats. In vitro, phenolic and flavonoid content and antioxidant activity were determined. In vivo, phenylhydrazine (10 mg/kg) was injected intravenously into rats for 4 days and then treated with apple vinegar daily by gavage (1 mL/kg) for five weeks. high level of polyphenols and flavonoids (90 ± 1.66 mg GAE/100 mL and 7.29 ± 0.23 mg QE/100 mL, respectively) were found in the apple vinegar which gives it a good ability to scavenge free radicals (TAC = 4.22 ± 0.18 mg AAE/100 mL and DPPH, IC₅₀ = 0.49 ± 0.004 µL/ml). The phytochemical composition of apple vinegar revealed the presence of numerous bioactive compounds including arbutin, apigenin, sinapic, ferulic and trans-ferulic acids. The major antioxidant components in apple vinegar were ferulic and trans-ferulic acids (40% and 43%, respectively). PHZ treatment induced changes in platelets, blood cell count, mean corpuscular volume, hemoglobin concentration and mean capsulated hemoglobin. However, the co-administration of apple vinegar revealed its capacity to ameliorate the changes induced by phenylhydrazine. Therefore, apple vinegar use could have a positive impact on the prevention of hemolytic anemia induced by phenylhydrazine due to the antioxidant properties of its major components. Full article