Investigating the Potential Anti-SARS-CoV-2 and Anti-MERS-CoV Activities of Yellow Necklacepod among Three Selected Medicinal Plants: Extraction, Isolation, Identification, In Vitro, Modes of Action, and Molecular Docking Studies.

The anti-MERS-CoV activities of three medicinal plants (Azadirachta indica, Artemisia judaica, and Sophora tomentosa) were evaluated. The highest viral inhibition percentage (96%) was recorded for S. tomentosa. Moreover, the mode of action for both S. tomentosa and A. judaica showed 99.5% and 92% inhibition, respectively, with virucidal as the main mode of action. Furthermore, the anti-MERS-CoV and anti-SARS-CoV-2 activities of S. tomentosa were measured. Notably, the anti-SARS-CoV-2 activity of S. tomentosa was very high (100%) and anti-MERS-CoV inhibition was slightly lower (96%). Therefore, the phytochemical investigation of the very promising S. tomentosa L. led to the isolation and structural identification of nine compounds (1−9). Then, both the CC50 and IC50 values for the isolated compounds against SARS-CoV-2 were measured. Compound 4 (genistein 4'-methyl ether) achieved superior anti-SARS-CoV-2 activity with an IC50 value of 2.13 µm. Interestingly, the mode of action of S. tomentosa against SARS-CoV-2 showed that both virucidal and adsorption mechanisms were very effective. Additionally, the IC50 values of S. tomentosa against SARS-CoV-2 and MERS-CoV were found to be 1.01 and 3.11 µg/mL, respectively. In addition, all the isolated compounds were subjected to two separate molecular docking studies against the spike (S) and main protease (Mpr°) receptors of SARS-CoV-2.

Appraisal on the Wound Healing Potential of Deverra tortuosa DC. and Deverra triradiata Hochst Essential Oil Nanoemulsion Topical Preparation.

Deverra tortuosa (Desf.) DC. and Deverra. triradiata Hochst. ex Bioss are perennial desert shrubs widely used traditionally for many purposes and they are characteristic for their essential oil. The objective of the present study was to investigate the in vivo wound healing activity of the essential oil (EO) of D. tortuosa and D. triradiata through their encapsulation into nanoemulsion. EO nanoemulsion was prepared using an aqueous phase titration method, and nanoemulsion zones were identified through the construction of phase diagrams. The EO was prepared by hydrodistillation (HD), microwave-assisted hydrodistillation (MAHD), and supercritical fluid extraction (SFE) and analyzed using GC/MS. D. tortuosa oil is rich in the non-oxygenated compound, representing 74.54, 73.02, and 41.19% in HD, MADH, and SFE, respectively, and sabinene represents the major monoterpene hydrocarbons. Moreover, D. triradiata is rich in oxygenated compounds being 69.77, 52.87, and 61.69% in HD, MADH, and SFE, respectively, with elemicin and myristicin as major phenylpropanoids. Topical application of the nanoemulsion of D. tortuosa and D. triradiata (1% or 2%) exhibited nearly 100% wound contraction and complete healing at day 16. Moreover, they exhibit significant antioxidant and anti-inflammatory effects and a significant increase in growth factors and hydroxyproline levels. Histopathological examination exhibited complete re-epithelialization accompanied by activated hair follicles and abundant collagen fibers, especially at a concentration of 2%. Therefore, the incorporation of the two Deverra species into nanoemulsion could professionally endorse different stages of wound healing.

Coriander (Coriandrum sativum L.) essential oil and oil-loaded nano-formulations as an anti-aging potentiality via TGFß/SMAD pathway.

Aging has become a concern for many people, especially women. Given that high-quality anti-aging products are of high cost; it has imperative to search for other economical sources. Essential oils are frequently used in cosmetics products due to a wide range of biological activities as well as their pleasant odor. The current study aimed to investigate the biochemical effect of the cosmetic potential of selected Apiaceous essential oils, traditionally used for skincare, by evaluating their anti-wrinkle activity. It is worth noting that, coriander essential oil showed the highest collagenase, elastase, tyrosinase, and hyaluronidase inhibitory activities compared to other Apiaceous oils (fennel, anise, and cumin). GC-MS proved that coriander essential oil showed a very high level of oxygenated monoterpenes, with linalool (81.29%) as the most abundant constituent. Intriguingly, coriander oil cream and Coriander Essential Oil-loaded Lipid Nanoparticles (CEOLNs) formulations attenuated in vivo UV-induced skin photoaging that was manifested by significantly decreased MDA, COX-2, PGE-2, MMP-1, JNK, and AP-1 levels. Moreover, these pharmaceutical dosage forms significantly increased skin collagen content compared to UV-injured group. Also, coriander essential oil significantly increased TGFß, TGFßII, and SMAD3 protein expression levels compared to UV-injured group. In conclusion, the pharmaceutical dosage forms of coriander oil possess anti-wrinkle activities that could have an auspicious role in amending extrinsic aging.

Protective effects of Saraca indica L. leaves extract (family Fabaceae) against gamma irradiation induced injury in the kidney of female albino rats.

This work was designed to estimate the protective effect of Saraca indica L. leaves ethanolic exract against γ-irradiation induced renal damage in rats. Phytochemical examinations of S. indica L. leaves extract resulted in the separation of three flavanone glycosides: Astilibin (1), Neoastilbin (2), and Eriodictyol-7-O-α-l-rhamnopyranoside (3); two flavonols: Quercetin (4) and Quercetin-3-O-α-l-arabinopyranosyl-(1'''-6'')-O-ß-D-galactopyranoside (5) in addition of Gallic acid (6) and methyl gallate (7). Their structures elucidated by chemical evidences and spectroscopic analysis (1 and 2D-NMR, -ESI-MS, UV). Female rats were used and classified into: control, Ext (200 mg/kg body wt/day orally for 7 days), IRR (8Gy), Ext + IRR, and Sily+IRR groups (received silymarin 50 mg/kg b.wt orally as reference drug). Results showed that S. indica L. leaves extract ameliorated the kidney function tests, hs-CRP, IL-1ß, ACE, TNF-α, GSH, and MDA as well as, decreased the histopathological changes of kidney. In conclusion, S. indica L. leaves extract had a renoprotective activity against irradiation induced renal injury due to its flavononid contents.

Bioactivity and biochemical efficacy of chitinase and Justicia brandegeana extract against Red Palm Weevil Rhynchophorus ferrugineus Olivier (Coleoptera: Curculionidae).

The red palm weevil Rhynchophorus ferrugineus is a large polyphagous insect, and this study was carried out to isolate chitinase from Beauveria bassiana as well as phytochemical screening of Justicia brandegeana to elucidate its effect as biocontrol agents against the red palm weevil and its possible effect on enzymatic bioactivity. It is the first time that the lipoid constituents of J. brandegeana were examined by both gas-liquid chromatography (GLC) and gas chromatography-mass spectrometry (GC/Mass). The results showed that the highest rates of mortality in treated prepupae were 35.0% and 30.0% with the higher concentration of chitinase (25 ppm) and petroleum ether extract of J. brandegeana (1,200 ppm), respectively. Moreover, changes in enzyme activity of ALP, PO, GPT, and GOT in the prepupal stage after treatment with LC50 chitinase and J. brandegeana extract were 36.63 & 14.32, -21.99 & 41.20, -11.02 & 47.05, and -36.00 & 21.43% compared with untreated control, respectively. This study demonstrated effectiveness of chitinase, and the petroleum ether extract of J. brandegeana has potent effect against Rh. ferrugineus due to its disturbance effect on the enzymatic system, protein as well as DNA damage.

Inhibition of SARS-CoV-2 main protease by phenolic compounds from Manilkara hexandra (Roxb.) Dubard assisted by metabolite profiling and in silico virtual screening.

SARS-CoV-2 is a novel coronavirus that was first identified during the outbreak in Wuhan, China in 2019. It is an acute respiratory illness that can transfer among human beings. Natural products can provide a rich resource for novel antiviral drugs. They can interfere with viral proteins such as viral proteases, polymerases, and entry proteins. Several naturally occurring flavonoids were reported to have antiviral activity against different types of RNA and DNA viruses. A methanolic extract of Manilkara hexandra (Roxb.) Dubard leaves is rich in phenolic compounds, mainly flavonoids. Metabolic profiling of the secondary metabolites of Manilkara hexandra (Roxb.) Dubard leaves methanolic extract (MLME), and bark ethyl acetate (MBEE) extract using LC-HRESIMS resulted in the isolation of 18 compounds belonging to a variety of constituents, among which phenolic compounds, flavones, flavonol glycosides and triterpenes were predominant. Besides, four compounds (I-IV) were isolated and identified as myricetin I, myricitrin II, mearnsitrin III, and mearnsetin-3-O-ß-d-rutinoside IV (compound IV is isolated for the first time from genus Manilkara) and dereplicated in a metabolomic study as compounds 3, 5, 6, and 12, respectively. The molecular docking study showed that rutin, myricitrin, mearnsitrin, and quercetin 3-O-ß-d-glucoside have strong interaction with SARS-CoV-2 protease with high binding energy of -8.2072, -7.1973, -7.5855, and -7.6750, respectively. Interestingly, the results proved that rutin which is a citrus flavonoid glycoside exhibits the strongest inhibition effect to the SARS-CoV-2 protease enzyme. Consequently, it can contribute to developing an effective antiviral drug lead against the SARS-CoV-2 pandemic.

Cardioprotective Effects of Spirulina Therapy in Children With Beta-Thalassemia Major.

INTRODUCTION: Cardiac failure in children with Thalassemia major (TM) is the major cause of death due to iron overload. Spirulina is a micro alga with proven anti-inflammatory, antioxidant and may have a cardioprotective effect. AIM OF THE WORK: The aim of this study was to evaluate the possible beneficial effect of spirulina supplement in TM children. SUBJECT AND METHODS: It is an interventional study carried out in 60 children with TM and 30 healthy children matched for age and sex as control. Both groups received spirulina supplement at a dose of 250 mg/kg/d for 3 months. 2D Echo, Tissue Doppler, and speckle tracking imaging (STI) were done for all the studied cohort before and after the 3-month duration of spirulina supplement. RESULTS: There was significant improvement in hemoglobin level at the end of 3-month period (8.27±1.3 vs. 9.023±1.7; P <0.033) with decrease the frequency of blood transfusion in TM patients (66.6% vs. 40% required transfusion at interval less than 2 wk). Left ventricle global longitudinal strain (LVGLS) significantly improved after 3-month period (-21.7±4.64 vs. -24.67±4.478; P <0.002). CONCLUSIONS: Spirulina supplement has possible beneficial effect in minimizing the frequency of blood transfusion as well as cardioprotective effect against cardiac damage in TM patients.

Thermal analysis of some antidiabetic pharmaceutical compounds.

PURPOSE: Thermal behavior of some antidiabetic drugs such as pioglitazone hydrochloride (PTZ), rosiglitazone maleate (RGZ), glibenclamide (GBD) and glimepiride (GMP) has been studied. METHODS: Thermogravimetric analysis (TGA), derivative thermogravimetry (DTG) and differential thermal analysis (DTA) techniques were used to study the thermal behavior of the drugs under investigation. RESULTS: Thermal analysis technique was used to obtain quality control parameters such as melting point 193.13 °C, 122.42 °C, 173.75 °C and 208 °C for PTZ, RGZ, GBD and GMP, respectively. The values of melting point of gave satisfactory results in comparison to that obtained by using the official method. Non-isothermal methods were employed to determine the activation energy values of the first stage of thermal decomposition. Comparison of the activation energy values suggests the following sequence of thermal stability: GMP > GBD > RGZ > PTZ. CONCLUSION: The results obtained are useful for the identification of these compounds and permitted interpretations concerning their thermal decomposition. Thermal stability of pharmaceutical compounds can be studied and compared by using thermal analysis techniques.

Lipophilic Constituents of Rumex vesicarius L. and Rumex dentatus L.

Rumex dentatus L. and Rumex vesicarius L., of the family Polygonaceae, are edible herbs growing wild in Egypt. Their lipoid constituents were examined by both liquid chromatography/mass spectrometry (LC/MS) and by gas chromatography/mass spectrometry (GC/MS). Their essential oil compositions consisted mainly of thujene, limonene, fenchon, estragole, and anethole but at largely different concentration. Fatty acid compositions were similar among the two species and consisting of palmitic, oleic, linoleic and linolenic acids, with R. vesicarius containing much higher level of omega-3-fatty acids. Both of the crude lipid extracts of the two species showed strong antioxidant activity as a radical quenching agent against 2,2-diphenyl-1-picrylhydrazyl (DPPH) systems. Antioxidant activities were mostly associated with the polar lipid fractions. High performance thin layer chromatography (HPTLC), both in the normal and reversed phase,as well as liquid chromatography/mass spectrometry (LC/MS) in the positive and negative electrospray ionization (ESI), showed unique chemical profile for each species that can be useful for species identification and quality control of herbal drug formulations. R. vesicarius was characterized by abundances of flavonoids and R. dentatus was abundant in anthraquinones and chromones.

Comparative efficacy and bioavailability of different praziquantel brands.

This study investigates the efficacy, bioavailability and drug metabolizing enzymes mainly involved in the metabolism of the commercial brands of praziquantel (PZQ) in Egypt in comparison with the original pure powder. Mice infected with PZQ-susceptible (CD) or PZQ-insusceptible (EE2) Schistosoma mansoni isolates were divided each into seven groups, six of them received PZQ brands (Distocide, Epiquantel, Biltricide, Bilharzid, Praziquantel, and pure PZQ), while the seventh one was left as infected untreated. Seven weeks post-infection, worms were quantified and hepatic CYP450 and CYT b5 were examined. For PZQ pharmacokinetics, groups of normal mice were given the different PZQ brands and divided into subgroups, killed at 2, 5, 15, 30, 60, 90, 120,150, 180, 240 and 360 min post-dosing. Physicochemical examination revealed better dissolution rates for Biltricide, Distocide and PZQ T3A rather than Epiquantel and Bilharzid. Significant decrease in worm burden was recorded in all groups of mice regardless of the brand of PZQ used, but with better results obtained with CD isolate rather than the EE2 isolate. Biltricide and Distocide showed higher C(max) and AUC(0-6h) in normal mice, in addition to higher worm reduction with least inhibition of CYP450 and CYT b5 in EE2-infected mice. PZQ T3A, Bilharzid and Epiquantel showed, in addition to lower efficacy, higher K(el), lower t(1/2e), C(max) and AUC(0-6h). The 32-46% reduction of their bioavailability reflected on their antischistosomal efficacy and recovery of drug metabolizing enzymes. Quality of generic PZQ should include, in addition to examining the physicochemical characteristics of the brands, biological testing including efficacy and bioavailability studies.

Isoflavonoid glycosides and rotenoids from Pongamia pinnata leaves.

Chromatographic separation of a 70% aqueous methanol extract (AME) of Pongamia pinnata (Linn.) Pierre (Leguminosae) leaves has led to the isolation of two new isoflavonoid diglycosides, 4'-O-methyl-genistein 7-O-beta-D-rutinoside (2) and 2',5'-dimethoxy-genistein 7-O-beta-D-apiofuranosyl-(1"'-->6")-O-beta-D-glucopyranoside (6), and a new rotenoid, 12a-hydroxy-alpha-toxicarol (5), together with nine known metabolites, vecinin-2 (1), kaempferol 3-O-beta-D-rutinoside (3), rutin (4), vitexin (7), isoquercitrin (8), kaempferol 3-O-beta-D-glucopyranoside (9), 11,12a-dihydroxy-munduserone (10), kaempferol (11), and quercetin (12). Their structures were elucidated on the basis of chemical and spectroscopic analyses.

Antioxidant flavonol glycosides from Schinus molle.

Chromatographic separation of aqueous MeOH extract of the leaves of Schinus molle L. has yielded two new acylated quercetin glycosides, named isoquercitrin 6''-O-p-hydroxybenzoate (12) and 2''-O-alpha-L-rhamnopyranosyl-hyperin 6''-O-gallate (13), together with 12 known polyphenolic metabolites for the first time from this species, namely gallic acid (1), methyl gallate (2), chlorogenic acid (3), 2''-alpha-L-rhamnopyranosyl-hyperin (4), quercetin 3-O-beta-D-neohesperidoside (5), miquelianin (6), quercetin 3-O-beta-D-galacturonopyranoside (7), isoquercitrin (8), hyperin (9), isoquercitrin 6''-gallate (10), hyperin 6''-O-gallate (11) and (+)-catechin (14). Their structures were established on the basis of chromatographic properties, chemical, spectroscopic (UV, 1H, 13C NMR) and ESI-MS (positive and negative modes) analyses. Compounds 4-9 and 11 exhibited moderate to strong radical scavenging properties on lipid peroxidation, hydroxyl radical and superoxide anion generations with the highest activities shown by 6 and 7 in comparison with that of quercetin as a positive control in vitro.