Disease-associated regulation of gene expression by resveratrol: Special focus on the PI3K/AKT signaling pathway.

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a natural phenol that is present in the skin of the grape, blueberry, raspberry, mulberry, and peanut. This substance is synthesized in these plants following injury or exposure to pathogens. Resveratrol is used as a dietary supplement for a long time and its effects have been assessed in animal models of human disorders. It has potential beneficial effects in diverse pathological conditions such as diabetes mellitus, obesity, hypertension, neoplastic conditions, Alzheimer's disease, and cardiovascular disorders. Notably, resveratrol has been found to affect the expression of several genes including cytokine coding genes, caspases, matrix metalloproteinases, adhesion molecules, and growth factors. Moreover, it can modulate the activity of several signaling pathways such as PI3K/AKT, Wnt, NF-κB, and Notch pathways. In the current review, we summarize the results of studies that reported modulatory effects of resveratrol on the expression of genes and the activity of signaling pathways. We explain these results in two distinct sections of non-neoplastic and neoplastic conditions.

Interplay between PI3K/AKT pathway and heart disorders.

The PI3K/AKT signaling has crucial role in the regulation of numerous physiological functions through activation of downstream effectors and modulation of cell cycle transition, growth and proliferation. This pathway participates in the pathogenesis of several human disorders such as heart diseases through regulation of size and survival of cardiomyocytes, angiogenic processes as well as inflammatory responses. Moreover, PI3K/AKT pathway participates in the process of myocardial injury induced by a number of substances such as H2O2, Mercury, lipopolysaccharides, adriamycin, doxorubicin and epirubicin. In this review, we describe the contribution of this pathway in the pathoetiology of myocardial ischemia/reperfusion injury and myocardial infarction, heart failure, cardiac hypertrophy, cardiomyopathy and toxins-induced cardiac injury.

The effects of Ginsenosides on PI3K/AKT signaling pathway.

Ginsenosides belong to a group of steroid glycosides that are extracted from the plant genus Panax (ginseng). This plant has been used for a long time for the treatment of a variety of disorders in traditional medicine. Recent studies have assessed the biological impact of Ginsenosides in cell culture or animal models. Animal studies have shown their beneficial impacts in the remedy of pathological conditions in different tissues. The ameliorating effects of Ginsenosides in diverse pathogenic conditions can be attributed to their effects on the production of reactive oxygen species. These substances mainly affect the activity of AMPK/AKT and PI3K/AKT pathways. The beneficial effects of Ginsenosides have been appraised in diabetes-related complications, spinal cord injury, cerebral ischemia, myocardial ischemia, and other disorders which are associated with oxidative stress. Moreover, these substances have been shown to interfere with the pathologic conditions during carcinogenesis. In the current study, we explain these impacts in two distinct sections including non-neoplastic conditions and neoplastic conditions.

Anthraquinones and Their Analogues from Marine-Derived Fungi: Chemistry and Biological Activities.

Anthraquinones are an interesting chemical class of polyketides since they not only exhibit a myriad of biological activities but also contribute to managing ecological roles. In this review article, we provide a current knowledge on the anthraquinoids reported from marine-derived fungi, isolated from various resources in both shallow waters such as mangrove plants and sediments of the mangrove habitat, coral reef, algae, sponges, and deep sea. This review also tentatively categorizes anthraquinone metabolites from the simplest to the most complicated scaffolds such as conjugated xanthone-anthraquinone derivatives and bianthraquinones, which have been isolated from marine-derived fungi, especially from the genera Apergillus, Penicillium, Eurotium, Altenaria, Fusarium, Stemphylium, Trichoderma, Acremonium, and other fungal strains. The present review, covering a range from 2000 to 2021, was elaborated through a comprehensive literature search using the following databases: ACS publications, Elsevier, Taylor and Francis, Wiley Online Library, MDPI, Springer, and Thieme. Thereupon, we have summarized and categorized 296 anthraquinones and their derivatives, some of which showed a variety of biological properties such as enzyme inhibition, antibacterial, antifungal, antiviral, antitubercular (against Mycobacterium tuberculosis), cytotoxic, anti-inflammatory, antifouling, and antioxidant activities. In addition, proposed biogenetic pathways of some anthraquinone derivatives are also discussed.

Highly selective fluorescent peptide-based chemosensors for aluminium ions in aqueous solution.

Two novel fluorescent peptide-based chemosensors, including A (2-amino-benzoyl-Ser-Glu-Glu-NH2) and B (2-amino-benzoyl-Ala-Glu-Pro-Glu-Ala-Glu-Pro-NH2) were synthesized and characterized by nuclear magnetic resonance (NMR) spectra. These fluorescent probes exhibited excellent selective and sensitive responses to Al3+ ions over other metal ions in aqueous buffered solutions. The limits of detection for both chemosensors towards the Al3+ ions were in the order of ∼10-7 M (A: 155 nM and B: 195 nM), which clearly indicates that these probes have significant potential for biological applications. They also displayed high binding affinity (1.3029 × 104 M-1 and 1.7586 × 104 M-1 relevant to A and B respectively). These two chemosensors are great analytical probes that produce turn-on responses upon binding to Al3+ ions through an intramolecular charge transfer (ICT) mechanism. In addition, the application of both chemosensors was examined over a wide range of pH. The fluorescent peptide-based probes and Al3+ form a 1:1 coordination complex according to the ESI-MS and Job's plot analysis. Notably, upon addition of Al3+ to these chemosensors, a fluorescence enhancement of approximately 8-fold was observed and the binding mode was determined using NMR titration and fluorescence emission data.

High-performance thin-layer chromatography fingerprinting and anti-inflammatory and antinociceptive activities of Pyracantha coccinea M.Roem.: A laboratory-based study.

This study aimed to investigate the high-performance thin-layer chromatography (HPTLC) fingerprinting and in-vivo anti-inflammatory and antinociceptive activities of different leaf extracts (ethanolic extract, n-hexane, chloroform, and ethyl acetate) of Pyracantha coccinea M.Roem. plant. A total of one hundred and twenty-four Wistar rats for anti-inflammatory and antinociceptive tests (carrageenan and formalin tests, respectively) were treated with two doses of the ethanolic extract (100 and 300 mg/kg), two doses of other plant fractions (30 and 100 mg/kg), Diclofenac (25 mg/kg) as the positive control, and normal saline as the negative control group, by oral gavage route. HPTLC fingerprinting is used for assay of terpenoids, flavonoids, alkaloids, and antioxidant activity. Treatment of the animal with the ethanolic extract at doses of 100 and 300 mg/kg, both ethyl acetate and chloroform fractions at the dose of 30 mg/kg and 100 mg/kg decreased the pain score in the formalin test and paw edema caused by carrageenan relative to control group significantly. Moreover, these extracts reported the highest amounts of flavonoid contents. In conclusion, phytochemicals present in Pyracantha coccinea M.Roem. leaves have anti-inflammatory and antinociceptive activities. Future studies are needed to identify the compounds with the anti-inflammatory and antinociceptive potential present in the plant.

LC-ESI-QTOF-MS/MS characterization of phenolic compounds from Prosopis farcta (Banks & Sol.) J.F.Macbr. and their potential antioxidant activities.

Prosopis farcta (Banks & Sol.) J.F.Macbr. is an emerging medicinal plant containing a diverse array of phytochemicals, including protein, fat, carbohydrate, fibre, alkaloids, fatty acids, glycosides, and polyphenols, with strong antioxidant potential. However, the screening and characterization of phenolic compounds in P. farcta is limited. This study is conducted to determine the polyphenol contents and their antioxidant activity in P. farcta leaves samples via liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF-MS/MS) and high-performance liquid chromatography-photodiode array (HPLC-PDA). Total phenolic content (TPC), total flavonoid content (TFC), and total tannins content (TTC) were determined for polyphenol estimation. The antioxidant properties were measured by total antioxidant capacity (TAC), 2,2'-Diphenyl-2-picrylhydrazyl (DPPH), Ferric Reducing Antioxidant Power (FRAP), and 2,2"²-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). LC-ESI-QTOF-MS/MS was used to identify and characterize 47 phenolic compounds, which mainly included phenolic acids (13), flavonoids (28), other polyphenols (4), lignans (1), and stilbenes (1). According to HPLC-PDA quantification, chlorogenic acid (9.78 ± 2.15 mg/g dw) was the most abundant phenolic acid, while the main flavonoids included catechin (12.73 ± 1.29 mg/g dw) and kaempferol (7.93 ± 1.47 mg/g dw). The study demonstrated the significance of P. farcta as a rich source of phenolic compounds with antioxidant capacity that can be widely used in food, beverage, feed, and pharmaceutical applications.

The efficacy of interferon-beta therapy in multiple sclerosis patients: investigation of the RORA gene as a predictive biomarker.

Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory neuronal damages and consequent disabilities. Episodic relapses of the disease which lead to brain lesions and irreversible neurological dysfunctions could be decreased by the interferon-beta (IFN-ß) therapy in most of the MS patients. However, the efficiency of the drug response is highly variable among patients and the precise mechanism of action of the IFN-ß is not clear. To investigate the role of RORA gene as a biomarker of patient's responsiveness, the present study have analyzed the frequency of two polymorphisms (rs4774388 and rs11639084) within this gene between responder (n = 105) and nonresponder (n = 65) groups of MS patients in comparison with 200 healthy controls. The tetra primers-Amplification Refractory Mutation System-PCR method was used for genotyping. The obtained result of the current study showed a significant association between nonresponsiveness and the rs4774388 in dominant model (p = 0.03). However, the allele and genotype frequencies of rs11639084 were not different between controls, nonresponder, and responder patients. In addition, the frequencies of the estimated haplotype blocks were not different between examined groups. The obtained results of the present study suggested the rs4774388 as a possible effective factor in determination of response to IFN-ß. However, further studies are needed to confirm the results in a larger sample size.

Phenolic compounds, saponins and alkaloids on cancer progression: emphasis on p53 expression and telomere length.

Telomere length is correlated with cell proliferation, and cancer cells are characterized by an uncontrolled cell cycle. Being apoptosis one of the checks and balances incorporated into cells cycle, due to its characteristics, cancer cells are able to overcome this process. In particular, the tumour suppressor protein p53 loss or inactivation can lead to activation of telomerase enzyme, which can make cells unable to detect DNA damages that spurs apoptosis. Some bioactive compounds, in particular phenolic compounds, saponins and alkaloids have revealed good abilities to affect p53 expression and indirectly control the telomere length. In this sense, this review gives a key emphasis to the ability of these compounds in blocking cancer progression by acting on p53 expression and controlling telomere length. As main findings, phenolic compounds, saponins and alkaloids interfere with cancer progression by stimulating p53 expression, which can cause pro-apoptotic onset and restrict the anti-apoptotic activity, in addition to preventing telomerase enzyme activity.

High-performance thin-layer chromatography fingerprinting, total phenolic and total flavonoid contents and anti-platelet-aggregation activities of Prosopis farcta extracts.

Cardiovascular diseases are a leading cause of worldwide death and excessive platelet is closely related with their pathogenesis. Different plants and natural compounds have demonstrated anti-platelet effects. The aim of this study was to report the high-performance thin-layer chromatography (HPTLC) fingerprinting and anti-platelet-aggregation activities of different leaf extracts (n-hexane, chloroform, ethyl acetate, methanol and aqueous) of Prosopis farcta (Syrian mesquite) plant. The results showed a 100% inhibition of aggregation activity after plasmatic adenosine diphosphate (ADP) aggregation activation of ethyl acetate, ethanolic, methanolic and aqueous extracts, at 60 mg/mL concentration. The IC50 ADP value of these extracts ranged between 4.07 and 11.39 mg/mL. Moreover, these extracts reported the highest amounts of phenolic and flavonoid contents. In conclusion, phytochemicals present in P. farcta leaves have anti-platelet-aggregation activities. Future studies are needed to identify the compounds with anti-platelet potential present in P. farcta.

Phytochemical screening of Alstonia venenata leaf and bark extracts and their antimicrobial activities.

Alstonia venenata is a plant commonly found in South India and used in traditional medicine. The aim of this study was to characterize the phytochemicals present in A. venenata leaf and bark extracts and study their antimicrobial activities. Solvent extractions with Soxhlet apparatus of leaves and bark were obtained using hexane, benzene, isopropanol, methanol, and water. The crude extracts were concentrated and screened for qualitative phytochemical content and analyzed by thin layer chromatography. The antibacterial, antifungal and antiviral activities of crude extracts were measured by in vitro methods. Alkaloids, carbohydrates, tannins, phenolic compounds, terpenoids, cardiac glycosides and amino acids were found in the different crude extracts analyzed. Isopropanol extracts showed antifungal activity and it was more pronounced in the bark extract than the leaf extract. Moreover, the isopropanol extract exhibited antibacterial and antiviral activity. In conclusion, the leaves and bark of A. venenata have antimicrobial components which are more present in the isopropanol fraction.

Phytol anti-inflammatory activity: Pre-clinical assessment and possible mechanism of action elucidation.

Phytol (PHY) is an acyclic natural diterpene alcohol and a chlorophyll constituent that exhibits several pharmacological effects, such as anticancer, antioxidant, and antimicrobial. Here, we aimed to assess the PHY anti-inflammatory effect in vitro and in vivo, and to deepen knowledge on the possible mechanism of action. For this purpose, egg albumin (in vitro) test was performed by using acetyl salicylic acid (ASA) as a standard nonsteroidal anti-inflammatory drugs (NSAID). For in vivo test, male Wistar albino rats were treated (intraperitoneally) with 100 mg/kg of PHY and/or standard NSAIDs ASA (100 mg/kg) and diclofenac sodium (Diclo-Na, 10 mg/kg) to evaluate the combined effect of PHY in formalin-induced paw edema model. Furthermore, an in silico (CADD) study was accomplished to assess the effect of PHY against cyclooxygenase (COX)-1 and 2 enzymes, nuclear factor kappa B (NF-κB), and interleukin-1ß (IL-1ß). Results revealed that PHY exhibits dose-dependent anti-inflammatory effect using the egg albumin method. PHY (100 mg/kg) co-treated with ASA and/or Diclo-Na reduced paw edema better than PHY alone or NSAIDs individual groups. Computational study showed that PHY efficiently interacts with COX-1 and 2, NF-κB, and IL-1ß. In conclusion, PHY exhibits anti-inflammatory activity, possibly via COX-1 and 2, NF-κB, and IL-1ß dependent pathways.

Phytochemical screening of Alstonia scholaris leaf and bark extracts and their antimicrobial activities.

Alstonia sholaris is an evergreen tree commonly found in South East Asia. In traditional medicine pharmacological activities are attributed to the leaves and bark of this plant. The aim of this study is characterizing the chemicals present in A. sholaris leaves and bark extracts and study their antimicrobial activities. Solvent extractions with Soxhlet apparatus of leaves and bark were obtained using hexane, benzene, isopropanol, methanol, and water. The crude extracts were concentrated and screened for qualitative phytochemical analysis and thin layer chromatography, and the antibacterial, antifungal an antiviral activity of crude extracts were measured by in vitro methods. Isopropanol and methanol extracts showed significant antibacterial activity and it was more pronounced against Gram positive than against Gram negative bacteria. Hexane, benzene, isopropanol and methanol fractions of A. scholaris bark and leaf showed activity against Enterobacter cloacae. Isopropanol extract showed maximum activity against selected human pathogenic fungus. In conclusion, the leaves and bark of A. scholaris are rich in phytochemicals with antimicrobial activities against human pathogens, being the isopropanol fraction the one with the highest antibacterial, antifungal, antiviral and anti-mycobacterial activities.

Biological activities and health-promoting effects of Pyracantha genus: a key approach to the phytochemical's potential.

Pyracantha spp. are commonly called firethorn, and attract human attention due to their colorful berries. These berries are eaten globally as a traditional remedy for treating different stomach abnormalities, and as a cooking ingredient for folk diets. The present review aims to provide an overview on Pyracantha genus' geographical distribution and botanical description, traditional uses, phytochemical composition, biological activities and safety issues. Several biological activities have been reported to Pyracantha species, namely antioxidant, anti-inflammatory, antimicrobial, larvicidal and cytotoxic properties, most of them attributed to the use of their fruits. Pyracantha species phytochemical composition reveal the presence of interesting bioactive molecules, such as pyracrenic acid and fortuneanosides. The currently reported biological activities to these plants derive from in vitro and in vivo studies, so that clinical trials are needed to confirm these preclinical results. Nonetheless, Pyracantha species can be suggested as a safe herb useful to develop future drug formulations and functional foods.

Chemical constituents from Parrotia persica- Structural derivatization and their potential prolyl endopeptidase inhibition activity.

The current study was aimed to evaluate the prolyl endopeptidase (PEP) inhibitory activity of glutinol (1), azadiradione (2), quercetin 3-O-ß-d-glactopyranoside (3), catechin (4), quercetin (5), naringenin (6) isolated from Parrotia persica C. A. Mey. Naringenin (6) was further derivatized into 7-O-propargylnaringenin (7), 4',6',4″-O-propargylchalcone (8), and 4',4″-O-propargylchalcone (9). All compounds 1-9 were evaluated for their PEP inhibition activity. PEP is associated with several diseases, including dementia, and Alzheimer's disease (AD). Azadiradione (2) was less active with IC50 = 356.80 ± 2.9 µM, whereas quercetin (5) showed a potent activity with IC50 = 37.12 ± 2.2 µM, as compared to IC50 = 125.00 ± 1.5 µM of standard drug bacitracin. Naringenin (6) was found to be inactive, whereas its new analogues 7-9 were identified as potent inhibitors of PEP with IC50 = 35.20, 41.20, and 29.60 µM, respectively. Kinetic studies of active compounds indicated their modes of inhibition. Compounds 7-9 were found to be mixed-type inhibitors, while compound 5 was found to be non-competitive inhibitor.

Interleukin (IL)-8 polymorphisms contribute in suicide behavior.

Previous studies have highlighted the role of immune dysregulation in suicide behavior. Interleukin (IL)-8 is a chemokine with neuroprotective effects whose lower serum concentrations have been detected in individuals committed suicide. In the present study, we genotyped three single nucleotide polymorphisms (SNPs) within IL-8 gene (rs4073, rs2227306 and rs1126647) in 229 individuals who attempted suicide with soft suicide methods, 235 suicide victims and 290 individuals without any history of psychiatric disorders or suicide attempt. The T allele of rs4073 was significantly over-represented in suicide attempt group compared with both control and completed suicide groups (adjusted P values of 8.3E-7 and 9.8E-8 respectively). This SNP was associated with suicide attempt in both dominant and co-dominant models (P values of 6.2E-9 and 4.3 E-8 respectively). The genotype and allele frequencies of other SNPs were not significantly different among the three study groups. The T C A haplotype (rs4073, rs2227306 and rs1126647 respectively) were significantly less prevalent in completed suicide group compared with suicide attempt group (OR (95% CI) = 0.63 (0.46-0.86), adjusted P value = 0.03). Besides, the A T A haplotype has significant lower frequency in individuals who attempted soft suicide compared with controls (OR (95% CI) = 0.44 (0.26-0.75), adjusted P value = 0.02). However, this haplotype was significantly more prevalent in individuals attempted hard methods compared with those attempted soft methods (OR (95% CI) = 2.21 (1.26-3.87), adjusted P value = 0.04). The present study provided further evidence for the role of IL-8 in suicide behavior.

Antibacterial activity of some Lamiaceae species against Staphylococcus aureus in yoghurt-based drink (Doogh).

Doogh is a dairy drinkable fermented product, whose shelf-life and quality is mostly affected by bacteria such as Staphylococcus spp.. This study investigated the antibacterial activity of essential oils (EOs) from Thymus vulgaris L., Mentha piperita L. and Ziziphora tenuior L., alone or in combination, against Staphylococcus aureus in industrial doogh. A three-level and three-variable face centered central composite design experiment was used. Results showed that EOs significantly inhibited S. aureus growth after 1 and 7 days of storage. According to the model, the maximum inhibition was obtained in the presence of 0.2% of EO, independently of the type, and no synergistic or additive effects were observed. Slightly lower S. aureus survivals were observed at the maximum concentration of Z. tenuior EO. In spite of the antimicrobial activity of these EOs, further research is needed to assess their performance in food matrix and, in particular, in dairy product.

Medicinal Plants Used in the Treatment of Human Immunodeficiency Virus.

Since the beginning of the epidemic, human immunodeficiency virus (HIV) has infected around 70 million people worldwide, most of whom reside is sub-Saharan Africa. There have been very promising developments in the treatment of HIV with anti-retroviral drug cocktails. However, drug resistance to anti-HIV drugs is emerging, and many people infected with HIV have adverse reactions or do not have ready access to currently available HIV chemotherapies. Thus, there is a need to discover new anti-HIV agents to supplement our current arsenal of anti-HIV drugs and to provide therapeutic options for populations with limited resources or access to currently efficacious chemotherapies. Plant-derived natural products continue to serve as a reservoir for the discovery of new medicines, including anti-HIV agents. This review presents a survey of plants that have shown anti-HIV activity, both in vitro and in vivo.

Short Communication - Synthesis of drug metal complexes and their influence on human platelet aggregation.

During the past few decades the emergence of inorganic medicinal chemistry has been developed novel therapeutic agents. Researcher's perseverance in this branch of chemistry has led them to explore further valuable chemical spaces by synthesizing metal complexes already known pharmacological agents for their potential use. However, it is in its early stage, this methodology has demonstrated metal complexes with better bioactivities than the parent ligand molecules. In this study, transition metal complexes of pyrazinamide (PZ), isoniazid (INH), fluconazole (FCZ), metformin (dimethylbiguanide, DMBG) and losartan potassium (LS-K) were selected to evaluate for their possible anti-platelets aggregation in the light of reports on divalent and trivalent cations like calcium, copper, manganese, magnesium, and cadmium may influence the process of thrombocytic activity and aggregation. The required evaluation was carried out on human plasma through an APACT 4004 platelet aggregation analyzer. Arachidonic acid (ADP) was used to gauge any alteration in platelet shape and aggregation process. The parent drugs showed some anti-platelets aggregation, however, their metal complexes demonstrated better efficacy.

Spectroscopic and cytotoxic studies of losartan complexes.

Use of drug-metal complexes for the treatment of several human diseases has resulted in significant progress in the field of medicinal inorganic chemistry. The current study describes the synthesis and characterization of Cu (II) and Ni (II) complexes of Losartan, an antihypertensive drug. These complexes were evaluated for their cytotoxic activity against four human cancer cell lines; SNB-19, HCT-15, COLO-205 and KB-3-1. Spectroscopic characterization revealed that during complex formation, the metal was bound through the nitrogen atoms of the tetrazole moiety of the losartan molecule. The molecular formulas of copper ([Cu (LS) 2 Cl2].6H2O) and nickel ([Ni (LS) 2Cl2]. H2O) complexes were found to be in agreement with the analytical data obtained through elemental analysis. For both the complexes, metal to ligand ratios of 1:2 were calculated. As revealed by FTIR, UV-Visible, and 1H-NMR studies, both the complexes displayed octahedral geometries. Scanning electron microscopy (SEM) revealed marked changes in the morphology of the complexes, compared to the pure drug. From XRD studies, characteristic crystalline peaks of pure losartan were observed whereas no prominent peaks were observed for its complexes. Complexes were found to be inactive in the cytotoxic activity test performed using SNB-19, HCT-15, COLO-205 and KB-3-1 cell lines.