Bio-Guided Assay of Ephedra foeminea Forssk Extracts and Anticancer Activities: In Vivo, In Vitro, and In Silico Evaluations.

Ephedra is one of the oldest known medicinal plants and the largest genera of the Ephedraceae family. In vivo antitumor evaluation of Ephedra foeminea revealed that ethyl acetate (EtOAc) was the most bioactive fraction. Bio-guided fractionation of EtOAc fraction afforded nine compounds isolated for the first time from the plant species. Macrocyclic spermine alkaloids (1,9), proanthocyanidins (2,4,5), quinoline alkaloids (7,8), phenolic (3), and nucleoside (6) were identified and elucidated by spectroscopic analyses including 1D and 2D NMR, ESI-MS-MS spectrometry. The tested compounds exhibited moderate anticancer activity, except for the kynurenic acid derivative (6-mKYNA) which showed significant cytotoxicity and remarkable inhibition of CA-19.9 and CA-125 tumor biomarkers. In-silico study was conducted to determine the anti-proliferative mechanism of 6-mKYNA by using the CK2 enzyme active site. Moreover, the ADME computational study suggested that 6-mKYNA is an effective candidate with a promising pharmacokinetic profile and therapeutic potential against various types of cancer.

Immunostimulant plant proteins: Potential candidates as vaccine adjuvants.

The COVID-19 pandemic is shaking up global scientific structures toward addressing antibiotic resistance threats and indicates an urgent need to develop more cost-effective vaccines. Vaccine adjuvants play a crucial role in boosting immunogenicity and improving vaccine efficacy. The toxicity and adversity of most adjuvant formulations are the major human immunization problems, especially in routine pediatric and immunocompromised patients. The present review focused on preclinical studies of immunoadjuvant plant proteins in use with antiparasitic, antifungal, and antiviral vaccines. Moreover, this report outlines the current perspective of immunostimulant plant protein candidates that can be used by researchers in developing new generations of vaccine-adjuvants. Future clinical studies are required to substantiate the plant proteins' safety and applicability as a vaccine adjuvant in pharmaceutical manufacturing.

Topical Nano Clove/Thyme Gel against Genetically Identified Clinical Skin Isolates: In Vivo Targeting Behavioral Alteration and IGF-1/pFOXO-1/PPAR γ Cues.

Antimicrobial resistance is a dramatic global threat; however, the slow progress of new antibiotic development has impeded the identification of viable alternative strategies. Natural antioxidant-based antibacterial approaches may provide potent therapeutic abilities to effectively block resistance microbes' pathways. While essential oils (EOs) have been reported as antimicrobial agents, its application is still limited ascribed to its low solubility and stability characters; additionally, the related biomolecular mechanisms are not fully understood. Hence, the study aimed to develop a nano-gel natural preparation with multiple molecular mechanisms that could combat bacterial resistance in an acne vulgaris model. A nano-emulgel of thyme/clove EOs (NEG8) was designed, standardized, and its antimicrobial activity was screened in vitro and in vivo against genetically identified skin bacterial clinical isolates (Pseudomonas stutzeri, Enterococcus faecium and Bacillus thuringiensis). As per our findings, NEG8 exhibited bacteriostatic and potent biofilm inhibition activities. An in vivo model was also established using the commercially available therapeutic, adapalene in contra genetically identified microorganism. Improvement in rat behavior was reported for the first time and NEG8 abated the dermal contents/protein expression of IGF-1, TGF-ß/collagen, Wnt/ß-catenin, JAK2/STAT-3, NE, 5-HT, and the inflammatory markers; p(Ser536) NF-κBp65, TLR-2, and IL-6. Moreover, the level of dopamine, protective anti-inflammatory cytokine, IL-10 and PPAR-γ protein were enhanced, also the skin histological structures were improved. Thus, NEG8 could be a future potential topical clinical alternate to synthetic agents, with dual merit mechanism as bacteriostatic antibiotic action and non-antibiotic microbial pathway inhibitor.

A Systemic Review on Aloe arborescens Pharmacological Profile: Biological Activities and Pilot Clinical Trials.

Since ancient times, plants and herbal preparations have been used as medicine. Research carried out in the last few decades has verified several such claims. Aloe arborescens Miller, belonging to the Aloe genus (Family Asphodelaceae), is one of the main varieties of Aloe used worldwide. The popularity of the plant in traditional medicine for several ailments (antitumor, immunomodulatory, antiinflammatory, antiulcer, antimicrobial and antifungal activity) focused the investigator's interest on this plant. Most importantly, the reported studies have shown the plant effectiveness on various cancer types such as liver, colon, duodenal, skin, pancreatic, intestinal, lung and kidney types. These multiple biological actions make Aloe an important resource for developing new natural therapies. However, the biological activities of isolated compounds such as glycoprotein, polysaccharides, enzyme and phenolics were insufficient. Considering all these, this contribution provides a systematic review outlining the evidence on the biological efficacy of the plant including the pharmacology and the related mechanisms of action, with specific attention to the various safety precautions, and preclinical and clinical studies, indicating the future research prospects of this plant.

Flaxseed oil fraction reverses cardiac remodeling at a molecular level: improves cardiac function, decreases apoptosis, and suppresses miRNA-29b and miRNA 1 gene expression.

Flaxseed is an ancient commercial oil that historically has been used as a functional food to lower cholesterol levels. However, despite its longstanding treatment, there is currently a lack of scientific evidence to support its role in the management of cardiac remodeling. This study aimed to address this gap in knowledge by examining the molecular mechanism of standardized flaxseed oil in restoring cardiac remodeling in the heart toxicity vivo model. The oil fraction was purified, and the major components were standardized by qualitative and quantitative analysis. In vivo experimental design was conducted using isoproterenol ISO (85 mg/kg) twice subcutaneously within 24 h between each dose. The rats were treated with flaxseed oil fraction (100 mg/kg orally) and the same dose was used for omega 3 supplement as a positive control group. The GC-MS analysis revealed that α-linolenic acid (24.6%), oleic acid (10.5%), glycerol oleate (9.0%) and 2,3-dihydroxypropyl elaidate (7%) are the major components of oil fraction. Physicochemical analysis indicated that the acidity percentage, saponification, peroxide, and iodine values were 0.43, 188.57, 1.22, and 122.34 respectively. As compared with healthy control, ISO group-induced changes in functional cardiac parameters. After 28-day pretreatment with flaxseed oil, the results indicated an improvement in cardiac function, a decrease in apoptosis, and simultaneous prevention of myocardial fibrosis. The plasma levels of BNP, NT-pro-BNP, endothelin-1, Lp-PLA2, and MMP2, and cTnI and cTn were significantly diminished, while a higher plasma level of Topo 2B was observed. Additionally, miRNA - 1 and 29b were significantly downregulated. These findings provide novel insight into the mechanism of flaxseed oil in restoring cardiac remodeling and support its future application as a cardioprotective against heart diseases.

Middle Eastern Plants with Potent Cytotoxic Effect Against Lung Cancer Cells.

Cancer is one of the leading causes of increasing global mortality with uprising health concerns and threats. Unfortunately, conventional chemotherapy has substantial side effects, limiting its relevance and prompting a quest for safe and efficient alternatives. For thousands of years, plants have provided a rich reservoir for curing a variety of ailments, including cancer. According to the World Health Organization, medicinal plants would be the best source of medications. However, only 25% of drugs in the present pharmacopoeia are derived from plants. Hence, further research into different plants is required to better understand their efficacy. Twenty extracts of widely distributed Middle Eastern plants were screened for the cytotoxic effect against lung cancer cell lines (A549). Eleven plants showed IC50 below 25 µg/mL, consequently, the bioactive extracts were further fractionated by graded precipitation using absolute ethanol. All fraction A (FA; crude polysaccharides precipitate) showed potent IC50, 0.2-5.5 µg/mL except the FA of Brassica juncea, Silybum marianum, and Phaseolus vulgaris, whereas FB fractions (filtrate) of Anastatica hierochuntica, Plantago ovate, Tussilago farfara, and Cucurbita moschata had lower efficacy than other fractions with IC50 values in the range of 0.1-7.7 µg/mL. The fractions of FA Taraxacum officinale and FB Ziziphus spina possess the most potent cytotoxic activity with IC50, 0.2 and 0.1 µg/mL, respectively. Moreover, cell cycle analysis of both fractions revealed an arrest at G1/S-phase and activation of apoptosis rather than necrosis as the mode of cell death. Therefore, T. officinale and Z. spina fractions may pave the way to manage lung carcinoma as an alternative and complementary food regimen.

Structural Elucidation of Immunomodulators, Acetylated Heteroglycan and Galactosamine, Isolated from Aloe arborescens Leaves.

Plant polysaccharides gained extended scientific attention for their immunomodulatory effect. However, few scientific studies structurally defined polysaccharides in relation to their biological modifier response. Therefore, the study explored the effect of structurally identified isolated macromolecules from Aloe arborescens against cytokine modulation (interferon [IFN-γ], interleukins [IL-2 and IL-12], and tumor necrosis factor [TNF-α]) in vitro. The structures were elucidated by GC, GPC, FT-IR spectroscopy, 1D NMR, COSY, HMBC, and HSQC. Two acetylated glucomannans (AANP4 and AAAP6), one deoxy-glucogalactan (AANP5), and one deoxy-N-acetyl-[1-4]-galactosamine (AANP2) were isolated. The results showed significant induction for all cytokines and the most potent component was AAAP6; acetylated phenolic glucomannan with a (1 → 3)-linked glucose-mannose and (1 → 4)-linked mannose backbone, which stimulated IL-12 by more than 10-fold compared with phytohemagglutinin (positive control). In conclusion, A. arborescens polysaccharides could be a landmark for development of effective immunotherapeutics against cancer and chronic inflammatory conditions.

Structural Characterization and In Vitro Cytokines Modulation Effect of New Acetylated Galactomannans from Aloe arborescens.

Three new galactomannan components designed as AANP-1, AANP-3, and AAAP-7 were isolated from previously purified Aloe arborescence polysaccharide fractions, using ion-exchange, gel filtration, and preparative chromatographic techniques. Based on Fourier transform-infrared, one-dimensional and two-dimensional nuclear magnetic resonance spectroscopy, the main backbone of AANP-1 elucidated as (1 → 4)-linked_α-d-deoxyGalp, (1 → 4) d-Manp, and ß-d-2-glup. The sugar residue sequence of AANP-3 was (1 → 4)-linked ß-d-NHAC-GAlp with ß-d-AcManp side chain that attached to O-4 position. The AAAP-7 repeated units were (1 → 4) d-Manp linked with (1 → 4) d-Galp interspersed with (1 → 3)-α-Manp. The results of high performance size-exclusion chromatography indicated that the approximate molecular weights of AANP-1, AANP-3, and AAAP-7 were 4.2, 2.4, and 2.5 kDa, respectively. The cytokine modulation assay revealed that the isolated components promoted a remarkable release of interleukin (IL)-12 and tumor necrosis factor alpha in comparison with the negative control group, whereas potent significant induction of IL-2 and interferon gamma was detected more than the positive control phytohemagglutinin (P < .05). This is the first report for isolation galactomannans from Aloe arborescence. Moreover, this finding could provide new insights for exploring the biological modifier mechanism in correlation with the knowledge of structural configuration.

Bioassay-guided isolation of potential bioactive constituents from pomegranate agrifood by-product.

Food industries are yielding annually plentiful by-products worldwide, these concomitants could be an excellent source of natural functional ingredients. Hence, the antimicrobial and cytotoxic effects of pomegranate husk were examined and chromatographic analyzes were applied for isolation of the bioactive compounds. Lignans; isohydroxymatairesinol, punicatannin C, flavonoids; phloretin, quercetin glycoside, indolamine; punigratane, and phenolic acid; coutaric acid were identified for the first time from pomegranate pericarp, and their structures were elucidated by spectroscopic analysis. Compared to isolated compounds, which showed a weak cytotoxic effects, punicatannin C induced a moderate cytotoxic activity against HepG2 and MCF-7 cell lines. Phloretin and coutaric acid exhibited potent antimicrobial activity againstStaphylococcus epidermidis,while punigratane possesses the most substantial antimicrobial effect onMicrococcus kristinae. In conclusion, pomegranate agrifood by-product; phloretin, punigratane, and coutaric acid display remarkablemicrobicideeffects and could be used in medical, cosmetic, and food industries purposes as a safe, and economical alternative to synthetic agents.

Chemical profile and antihyperlipidemic effect of Portulaca oleracea L. seeds in streptozotocin-induced diabetic rats.

Hypolipidemic effect of Portulaca oleracea L. seed extract and its fractions have been studied on streptozotocin (STZ) at dose 75 mg/kg b.wt. After fractionation of the alcoholic extract; petroleum ether fraction was the most active fraction that decreased different hyperlipidemia biochemical parameters. After chromatographic analysis; oleamide, ethylpalmitate, ß-amyrin, stigmasterol and ß-sitosterol were identified. The GLC analysis of unsaponifiable matter revealed the presence of; lignoceric acid as a major constituent in the most bioactive fraction. In conclusion, petroleum ether fraction possessed a hypolipidemic effect in STZ-induced diabetic rats, which may be attributed to its phytosterols, fatty acid and amide compounds. The finding of the present investigation strongly demonstrates the potential of non-polar fraction of P. oleracea L. seed in combating hyperlipidemia in diabetic condition. So the petroleum ether fractions and its constituents can be used as hypolipdemic supplement in the developing countries towards the development of new therapeutic agents.

Chromatographic separation and detection methods of Aloe arborescens Miller constituents: A systematic review.

Aloe arborescens Miller (Family Asphodelaceae) is a member of genus Aloe, which is used in traditional medicine to cure various diseases. The extracts of the plant have been reported to possess anticancer, immunomodulator, antidiabetic, anti-inflammatory and antioxidant activities. The phytochemical investigations have revealed diverse chemical constituents, including phenolics [anthraquinones, anthrones, pyrones, chromones and coumarins], polysaccharides [arborans [(1-4) linked glucomannans, polysaccharide (A, B and C): (A: a linear (1-6)-O-α-glucan, B: a branching (1-2)-O-l-arabinose with (1-2)-O-d-galactose linkages and C: (1-4)-O-ß-mannan with 18% acetyl group)]], glycoproteins and carboxypeptidase enzyme. There are many reports, describing the different methodologies developed to perform chemical analysis as well as, separation, detection and identification of these constituents. Different chromatographic techniques were applied such as gas chromatography (GC), high-performance liquid chromatography (HPLC), liquid chromatography-electrospray ionization coupled with mass spectroscopy (LC-ESI/MS/MS) and gel filtration chromatography. Also the isolated compounds were identified based on the spectroscopic analysis; ultraviolet-visible spectroscopy (UV-vis), infra-red spectroscopy (IR), mass spectroscopy (MS) and nuclear-magnetic resonance (NMR). This study aims to pinpoint the active components besides finding out new structural leads for future drugs. Therefore, the review is targeted to provide evidence reported in the relevant literature on qualitative and quantitative research to assist scientists in isolation and characterization of bioactive compounds in A. arborescens.

Aloe arborescens Polysaccharides: In Vitro Immunomodulation and Potential Cytotoxic Activity.

Different polysaccharides were isolated from the leaves of Aloe arborescens using the gradient power of hydrogen followed by antitumor and immunomodulatory assay. The total polysaccharide content of different fractions, water-soluble polysaccharide (WAP), acid-soluble polysaccharide (ACP), and alkaline-soluble polysaccharide (ALP), was estimated using a phenol-sulfuric acid spectrophotometric method. WAP possessed a higher content of mannose and glucose than either ACP or ALP. In vitro antitumor activity was investigated in three different cancer cell lines, and in vitro immunomodulatory potential was assessed through phagocytosis and lymphocyte transformation assay. The results showed that WAP and ALP exhibited the most significant cytotoxicity against HepG2 human liver cancer cells, with IC50 values of 26.14 and 21.46 µg/mL, respectively. In contrast, ALP was able to enhance lymphocyte transformation, whereas WAP had the most potent phagocytic activity. Molecular weight, total sugar and uronic acid content, Fourier transform-infrared analysis, and linkage type of bioactive polysaccharides were investigated. These findings revealed that the potential antitumor activity of the natural agents WAP and ALP was through an immunomodulation mechanism, which verifies the use of the plant as adjuvant supplement for cancer patients suffering immunosuppression during chemotherapy.