Natural Immunomodulatory Agents as a Complementary Therapy for Poxviruses.

Poxviruses target innate immunity mediators such as tumor necrosis factors, interleukins, interferons, complement, and chemokines. It also targets adaptive immunity such as CD4+ T cells, CD4+ T cells, and B cells. Emerging of the recent epidemic of monkeypox virus (MPXV), a zoonotic disease native to Central and Western Africa, besides the lack of permitted treatments for poxviruses infections, encouraged researchers to identify effective inhibitors to help in preventing and treating poxviruses infections. Natural bioactive components, particularly polyphenolics, are promising for creating powerful antioxidants, anti-inflammatory, immune-stimulating, and antiviral agents. As a result, they are potentially effective therapies for preventing and treating viral diseases, such as infections caused by poxviruses including the recent pandemic MPXV. Polyphenolics: rosmarinic acid, caffeic acid, resveratrol, quercitrin, myricitrin, gingerol, gallotannin, and propolis-benzofuran A, as well as isoquinoline alkaloids: galanthamine and thalimonine represent prospective antiviral agents against MPXV, they can inhibit MPXV and other poxviruses via targeting different viral elements including DNA Topoisomerase I (TOP1), Thymidine Kinase (TK), serine/threonine protein kinase (Ser/Thr kinase), and protein A48R. The bioactive extracts of different traditional plants including Guiera senegalensis, Larrea tridentata, Sarracenia purpurea, Kalanchoe pinnata (Lam.) Pers., Zingiber officinale Roscoe, Quercus infectoria, Rhus chinensis, Prunella vulgaris L., Salvia rosmarinus, and Origanum vulgare also can inhibit the growth of different poxviruses including MPXV, vaccinia virus (VACV), variola virus, buffalopox virus, fowlpox virus, and cowpox virus. There is an urgent need for additional molecular studies to identify and confirm the anti-poxviruses properties of various natural bioactive components, especially those that showed potent antiviral activity against other viruses.

Growth performance, blood biochemistry, and mRNA expression of hepatic heat shock proteins of heat-stressed broilers in response to rosemary and oregano extracts.

The growing interest in countering the adverse effects of heat stress in poultry using phytogenic feed additives has garnered considerable attention in recent times, this research sought to examine the impact of rosemary leaves extract (RLE) and oregano leaves extract (OLE) on the growth performance, physiological responses, and hepatic mRNA expression of heat shock proteins in broiler chickens exposed to heat stress. A total of 150 male Indian River chicks, aged one day, were randomly allocated into five equally sized groups, each consisting of six replicates. The initial group was designated as the control and was provided with the basal diet. The second and third groups (R1 and R2) were administered the basal diet enriched with 50 and 100 mg/kg of rosemary leaves extract (RLE), respectively. The fourth and fifth groups (O1 and O2) were fed the basal diet supplemented with 50 and 100 mg/kg of oregano leaves extract (OLE), respectively. These chicks were reared in a controlled environmental chamber maintained at a temperature of 32±2 °C and relative humidity of 50 ± 5 %. Ferruginol was the leading component in RLE, whereas thymol was the prevalent constituent in OLE. RLE and OLE both have high DPPH• and ABTS•+ antioxidant potential. Among the experimental groups, the fourth group (O1) showed the heaviest live body weight and the lowest feed conversion ratio, indicating improved growth performance. There was a significant reduction in plasma total lipids and LDL-cholesterol levels within the R2 and O2 groups, respectively. Enhanced total antioxidant capacity and an improvement in the T3 hormone were observed in the R1 and R2 groups. In the second and fourth groups, the mRNA expression of hsp70 and 90A were both found to be significantly downregulated, respectively. In conclusion, the addition of 50 mg/kg of oregano leaves extract (OLE) to the diets of heat-stressed broilers resulted in improved hepatic heat shock proteins, along with certain physiological responses, ultimately contributing to enhanced growth performance.

Natural ß-carotene prevents acute lung injury induced by cyclophosphamide in mice.

IL-17 is associated with varied inflammatory and immune-related diseases. However, the biological function of IL-17 and its expression in acute lung damage are not entirely known. Thanks to the powerful antioxidant properties of ß-carotene, we presumed that it would show a potent protecting effect against cyclophosphamide (CP) -induced acute lung injury (ALI) in mice. We studied the mechanisms underlying the effect of ß-carotene supplementation against CP-induced ALI in mice. We isolated the ß-carotene from Scenedesmus obliquus microalgae n-hexane extract and identified it by HPLC and 1H-NMR analysis. Within the experiments, 40 mice were assigned into five groups randomly: Group 1 (Control): Mice received saline. Group 2 (ß-carotene control): Mice were administered ß-carotene (40 mg/kg; orally) once daily for 10 sequent days without CP injection. Group 3 (CP): One i.p injection of 200 (mg/kg) of CP was given to mice. Group 4 and 5 (CP + ß-carotene): Mice were administered ß-carotene (20 and 40 mg/kg; orally) once a day for ten days following the CP injection. Lung samples were collected for lab analysis, after scarifying the animals at the experiment end. Administration of ß-carotene orally reduced CP-induced ALI and inflammation. ß-carotene significantly decreased wet-to-dry weight ratios (W/D), down-regulated IL-17, NF-κB, and IKBKB, decreased the contents of TNF-α, COX-2, and PKC, and increased the contents of SIRT1 and PPARγ in the lung tissues. ß-carotene ameliorated the histopathological changes induced by CP and reduced the scoring number of inflammatory cell infiltration and emphysema when compared to CP. Consequently, we conclude natural ß-carotene is a promising anti-inflammatory mediator for different inflammatory-related complications.

Lutein isolated from Scenedesmus obliquus microalga boosts immunity against cyclophosphamide-induced brain injury in rats.

Lutein is a naturally potent antioxidant carotenoid synthesized in green microalgae with a potent ability to prevent different human chronic conditions. To date, there are no reports of the immune-stimulating effect of pure lutein isolated from Scenedesmus obliquus. Thus, we isolated the natural lutein from S. obliquus and evaluated its effectiveness as an immunostimulant against cyclophosphamide-induced brain injury. We purified all-E-(3R, 3'R, 6'R)-Lutein from S. obliquus using prep-HPLC and characterized it by 1H- and 13C-NMR spectroscopy. We assigned rats randomly to four experimental groups: the Control group got a vehicle for lutein dimethyl sulfoxide for ten successive days. The Cyclophosphamide group received a single i.p injection of Cyclophosphamide (200 mg/kg). Lutein groups received 50 and 100 (mg/kg) of lutein one time per day for ten successive days after the cyclophosphamide dose. Lutein administration reduced brain contents of Macrophage inflammatory protein2 (MIP2), cytokine-induced- neutrophil chemoattractant (CINC), and Matrix metalloproteinase 1 (MMP1). Besides, it lowered the contents of interleukin 1 beta (IL-1ß) and interleukin 18 (IL-18), associated with low content of NLR pyrin domain protein 3 (NLRP3) and consequently caspase-1 compared to the cyclophosphamide group. In the histomorphometric analysis, lutein groups (50 and 100 mg/Kg) showed mild histopathological alterations as they significantly reduced nuclear pyknosis numbers by 65% and 69% respectively, compared to the cyclophosphamide group. This is the first study that showed the immunomodulatory roles of lutein against cyclophosphamide-induced brain injury via decreasing neuroinflammation, chemokines recruitment, and neuron degeneration with the modulation of immune markers. Hence, lutein can be an effective immunomodulator against inflammation-related immune disorders.

Haematococcus pluvialis Carotenoids Enrich Fractions Ameliorate Liver Fibrosis Induced by Thioacetamide in Rats: Modulation of Metalloproteinase and Its Inhibitor.

Hepatic fibrosis is a consequence of chronic liver diseases. Metalloproteinase and its inhibitor have crucial roles in the resolution of liver fibrosis. The current relevant study is aimed to evaluate the therapeutic effect of Haematococcus pluvialis (H. pluvialis) extract, astaxanthin-rich fraction, astaxanthin ester-rich fraction, and ß-carotene-rich fraction as well as their mechanisms of action in curing hepatic fibrosis induced by thioacetamide (TAA). Liver fibrosis was induced using TAA (intraperitoneal injection, two times a week for 6 weeks), in a rat model and H. pluvialis extract (200 mg/kg), and other fractions (30 mg/kg) were orally administered daily for 4 weeks after the last TAA injection. Based on HPLC analysis, H. pluvialis extract contains ß-carotene (12.95 mg/g, extract) and free astaxanthin (10.85 mg/g, extract), while HPLC/ESI-MS analysis revealed that H. pluvialis extract contains 28 carotenoid compounds including three isomers of free astaxanthin, α or ß-carotene, lutein, 14 astaxanthin mono-esters, 5 astaxanthin di-esters, and other carotenoids. H. pluvialis and its fractions reduced liver enzymes, nitric oxide, collagen 1, alpha-smooth muscle actin, and transforming growth factor-beta as well as elevated catalase antioxidant activity compared to the TAA group. Also, H. pluvialis extract and its fractions exceedingly controlled the balance between metalloproteinase and its inhibitor, activated Kupffer cells proliferation, and suppressed liver apoptosis, necrobiosis, and fibrosis. These findings conclude that H. pluvialis extract and its fractions have an antifibrotic effect against TAA-induced liver fibrosis by regulating the oxidative stress and proinflammatory mediators, suppressing multiple profibrogenic factors, and modulating the metalloproteinase and its inhibitor pathway, recommending H. pluvialis extract and its fractions for the development of new effective medicine for treating hepatic fibrosis disorders.

Ascorbic Acid Induces the Increase of Secondary Metabolites, Antioxidant Activity, Growth, and Productivity of the Common Bean under Water Stress Conditions.

One of the most vital environmental factors that restricts plant production in arid and semi-arid environments is the lack of fresh water and drought stress. Common bean (Phaseolus vulgaris L.) productivity is severely limited by abiotic stress, especially climate-related constraints. Therefore, a field experiment in split-plot design was carried out to examine the potential function of ascorbic acid (AsA) in mitigating the adverse effects of water stress on common bean. The experiment included two irrigation regimes (100% or 50% of crop evapotranspiration) and three AsA doses (0, 200, or 400 mg L-1 AsA). The results revealed that water stress reduced common bean photosynthetic pigments (chlorophyll and carotenoids), carbonic anhydrase activity, antioxidant activities (2,2-diphenyl-1-picrylhydrazyl free radical activity scavenging activity and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation assay), growth and seed yield, while increased enzymatic antioxidants (peroxidase), secondary metabolites (phenolic, flavonoids, and tannins), malondialdehyde (MDA), and crop water productivity. In contrast, the AsA foliar spray enhanced all studied traits and the enhancement was gradual with the increasing AsA dose. The linear regression model predicted that when the AsA dose increase by 1.0 mg L-1, the seed yield is expected to increase by 0.06 g m-2. Enhanced water stress tolerance through adequate ascorbic acid application is a promising strategy to increase the tolerance and productivity of common bean under water stress. Moreover, the response of common bean to water deficit appears to be dependent on AsA dose.

Chemical ingredients and antioxidant activities of underutilized wild fruits.

This study evaluated nutritional values, bioactive constituents and antioxidant activities of the five wild underutilized fruits in the mountains of southwest Saudi Arabia (Coccinia grandis (L.) Voigt, Diospyros mespiliformis Hochst. Ex A.Dc., Cissus rotundifolius (L.), Ephedra foeminea Forssk., and Grewia villosa Willd.). The moisture content, crude fibers, total protein, total lipids, total hydrolyzable carbohydrate, total soluble sugars, and total free amino acids were analyzed. The results showed varying amounts among fruits of the five study species. In addition, the mineral composition, amino acid content, phenolic compounds, vitamins, and antioxidant activity were assessed. The highest content of total phenolic and total tannins was measured in D. mespiliformis (20.69 mg/g and 3.84 mg/g) and the lowest in E. foeminea (10.83 mg/g and 1.44 mg/g), respectively. The methanol extract (1 mg/ml) of D. mespiliformis displayed higher percentage of DPPH radical scavenging activity (87.36%). The methanol extract (1 mg/ml) of C. grandis exhibited the highest effect of total antioxidant activity and hydrogen peroxide scavenging activity (71.53%). The sufficient nutritional and antioxidant value of these wild fruits provide healthy food source for the local residents, much the same as many cultivated fruits and vegetables.

Major constituents of Boswellia carteri resin exhibit cyclooxygenase enzyme inhibition and antiproliferative activity.

Aromatic gum from Boswellia carteri (olibanum oleogum) has long been used in Egyptian traditional medicine. Cyclooxygenase-1 (COX-1) enzyme inhibitory assay guided purification of the extracts of this resin resulted in five bioactive compounds, 3alpha-O-acetyl-8,24-dien-tirucallic acid (1), verticilla-4(20),7,11-triene (2), cembrene A (3), incensole acetate (4), and incensole (5). The pure isolates were investigated for their inhibitory effects on COX-1 and -2 enzymes and human tumor cell lines Hep-G2, MCF-7 and RAW 264.7. Compounds 1-5 inhibited COX-2 enzyme by 39.0, 32.7, 60.0, 46.3, and 49.8%, respectively. Furthermore, compound 2 showed an inhibitory concentration of 50% (IC50) at 9 microg/mL against Hep-G2 tumor cell line. This is the first report of COX-1 and -2 enzyme and tumor cell proliferation inhibitory effects of compounds 1 and 2.

Antioxidant and antibacterial activities of crude extracts and essential oils of Syzygium cumini leaves.

This research highlights the chemical composition, antioxidant and antibacterial activities of essential oils and various crude extracts (using methanol and methylene chloride) from Syzygium cumini leaves. Essential oils were analyzed by gas chromatography-mass spectrometry (GC-MS).The abundant constituents of the oils were: α-pinene (32.32%), ß-pinene (12.44%), trans-caryophyllene (11.19%), 1, 3, 6-octatriene (8.41%), delta-3-carene (5.55%), α-caryophyllene (4.36%), and α-limonene (3.42%).The antioxidant activities of all extracts were examined using two complementary methods, namely diphenylpicrylhydrazyl (DPPH) and ferric reducing power (FRAP). In both methods, the methanol extract exhibited a higher activity than methylene chloride and essential oil extracts. A higher content of both total phenolics and flavonoids were found in the methanolic extract compared with other extracts. Furthermore, the methanol extract had higher antibacterial activity compared to methylene chloride and the essential oil extracts. Due to their antioxidant and antibacterial properties, the leaf extracts from S. cumini may be used as natural preservative ingredients in food and/or pharmaceutical industries.