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UPLC-PDA-ESI/MS metabolic profiling of dill shoots bioactive fraction; evidence of its antioxidant and hepatoprotective effects in vitro and in vivo., Rasheed, Dalia M., Emad Ayat M., Ali Sherifa F., Ali Sameh S., Farag Mohamed A., Meselhy Meselhy R., and Sattar Essam A. , Journal of food biochemistry, p.e13741, (2021) Abstract

Hydroxyl radical ( OH) scavenging capacity of aqueous dill (Anethum graveolens L.) shoot (ADSh) extract was assessed using electron paramagnetic resonance (EPR) spectroscopy. ADSh extract (at concentrations of 0.5 and 10 mg/ml) exerted high (OH) radical scavenging power. ADSh extract was further fractionated on Diaion HP-20 column to yield five fractions. EPR spin-trapping assay revealed fraction 4 (eluted with 75% aq. MeOH) to possess ( OH) radical scavenging capacity over a concentration range (0.01-10 mg/ml), whereas fraction 2 (eluted with 25% aq. MeOH) appeared to be pro-oxidant at concentration 0.01 mg/ml. UPLC-PDA-ESI-MS metabolite profiling of ADSh extract revealed 87 metabolites, of which 64 compounds were identified in fraction 4, the most active fraction. Furthermore, ADSh extract demonstrated a hepatoprotective effect against acetaminophen (APAP)-induced hepatotoxicity in rats. Pretreatment of rats with ADSh extract (200 mg/kg b.wt) markedly attenuated the increased in the serum hepatic enzyme levels. It also increased free glutathione level and total antioxidant capacity in the serum of treated rats. [Correction added on May 3, 2021, after first online publication: "rates" has been changed to "rats" in the previous sentence.] Additionally, levels of (TNF-α and IL-1β) were back to almost normal levels compared to the control group. The above findings suggest that ADSh extract has a protective effect against APAP-induced liver damage.

UPLC-Orbitrap HRMS metabolic profiling of Cymbopogon citratus cultivated in Egypt; neuroprotective effect against AlCl-induced neurotoxicity in rats., Madi, Yasmine F., Choucry Mouchira A., El-Marasy Salma A., Meselhy Meselhy R., and El-Kashoury El-Sayeda A. , Journal of ethnopharmacology, Volume 259, p.112930, (2020) Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Cymbopogon citratus (lemongrass) is commonly used in teas, soups and treat inflammatory-based ailments, vascular and nervous disorders.

AIM OF THE STUDY: The study aimed to evaluate the neuroprotective effect of Cymbopogon citratus leaves through scientific protocol. The effect of aqueous (AE) and ethanolic (EE) extracts was evaluated against AlCl-induced Alzheimer's disease (AD) in rats. Metabolic profiling of the plant, isolation of bioactive compounds and standardization of the active fraction were investigated.

MATERIALS AND METHODS: AE of Cymbopogon citratus leaves was prepared as per traditional method (infusion), EE was prepared by repeated maceration in 90% ethanol, bioactive fraction (BAEE) was obtained from EE and the active compounds thereof were obtained by column chromatography. Metabolic profiling of Cymbopogon citratus was performed by UPLC-Orbitrap HRMS and HPLC was used for standardization. AlCl-induced Alzheimer's rats were used to assess neuroprotective effect of the extracts. Neuroprotective mechanism(s) of Cymbopogon citratus extracts was clarified through histopathological examination of brain tissues, estimation of AD biochemical markers, oxidative stress and neuroinflammation in brain homogenates. In addition, antioxidant (using DPPH assay) and anticholinesterase (using modified Ellman's method) activities were investigated.

RESULTS: AlCl-treated rats (17 mg/kg/day) showed histopathological alteration in brain tissues together with elevated levels of Aβ, tau proteins, MDA, NF-kB and IL-6. However, treatment with AE and EE of Cymbopogon citratus leaves prevented the pathological changes and maintained the levels of oxidative stress and inflammatory markers. In addition, BAEE significantly inhibited acetylcholinesterase enzyme (2.11 ± 0.11 mg/ml) and exhibited a strong antioxidant activity (24.99 ± 0.00 μg/ml). UPLC-MS of Cymbopogon citratus leaves showed peaks for twenty-eight compounds, twenty-one of them were identified. Three flavonoids; isoorientin, isoschaftoside and luteolin-7-O-neohesperidoside were isolated from BAEE as major constituents. The powdered leaves of Cymbopogon citratus was found to contain remarkable amounts of caffeic acid (3.49 mg/g dry wt.) and isoorientin (7.37 mg/g dry wt.) as determined by HPLC.

CONCLUSION: Cymbopogon citratus ethanolic extract attenuates AlCl-induced neurotoxicity in rats through inhibition of oxidative stress and inflammatory markers. This effect could possibly attributed, in part to its high content of phenolic acids and flavonoids. Accordingly, we recommend Cymbopogon citratus leaves for protection against AD.

Three new α-glucosidase inhibitors from guggul, the oleogum resin of Commiphora wightii., El-Mekkawy, Sahar, Meselhy Meselhy R., Nkobole Nolitha, and Lall Namrita , Natural product research, 2013, Volume 27, Issue 2, p.146-54, (2013) Abstract

Three new compounds; epi-mukulin, (Z)-Δ(1,2) dehydroguggulsterone and Δ(6,7)dehydro-20-hydroxygugglsterone were isolated from the n-hexane-soluble fraction (HSF) of the methanol extract of guggul, the oleogum resin of Commiphora wightii together with six known compounds: diasesartemin, (+)-epi-magnolin, (+)-diayangambin, gugglsterol I, (E)-guggulsterone and (Z)-guggulsterone. Their structures were elucidated on the basis of different spectroscopic data. α-Glucosidase inhibitory effects of HSF and the isolated compounds were evaluated calorimetrically. The HSF showed significant α-glucosidase inhibitory effect [IC(50) value of 140 µg mL(-1) (p < 0.05)]. Under the assay conditions, diasesartemin (IC(50) = 60.6 ± 0.01 µM) was found to be more potent than the positive control, acarbose (IC(50) = 92.94 ± 0.01 µM); a known α-glucosidase inhibitor (p < 0.05). The IC(50) values of epi-mukulin and (Z)-guggulsterone were found to be 159.33 and 132.14 µM, respectively. Other compounds showed weak α-glucosidase inhibitory effects, <30% inhibition of the enzyme activity at 0.1 mg mL(-1).

Three new α-glucosidase inhibitors from guggul, the oleogum resin of Commiphora wightii, El-Mekkawy, Sahar, Meselhy Meselhy R., Nkobole Nolitha, and Lall Namrita , Natural product research, Volume 27, Issue 2, p.146-154, (2013) Abstract
Synthetic E-guggulsterone derivative GSD-1 inhibits NF-κB signaling and suppresses the metastatic potential of breast cancer cells., Abdellatef, Amira A., Zhou Yue, Yamada Akane, Elmekkawy Sahar A., Kohyama Aki, Yokoyama Satoru, Meselhy Meselhy R., Matsuya Yuji, Sakurai Hiroaki, and Hayakawa Yoshihiro , Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, Volume 140, p.111737, (2021) Abstract

Guggulsterone (GS) [4,17(20)-pregnadiene-3,16-dione], is the main active phytosterol constituent in guggul, the gum resin of Commiphora wightii (Arnott.) Bhand./Commiphora mukul Engl. tree, and is known for its medicinal effects. In this study, we report that GSD-1, a structurally-related synthetic GS derivative, strongly inhibits NF-κB activation induced by TNF-α. GSD-1 prevented the nuclear translocation of p65 through the blockade of IκBα degradation and p65 phosphorylation, and further inhibited the activation of upstream kinases, including transforming growth factor-β activated kinase 1 (TAK1), IκB kinase (IKK) α, and IKKβ. Furthermore, GSD-1 inhibited the cell-intrinsic activation of NF-κB, and exerted its direct anti-cancer and anti-metastatic effects in both murine and human breast cancer cell lines. This study demonstrated GSD-1 to be an attractive compound to target NF-κB activation that has potential for treating breast cancer growth and metastasis.

Synthesis of guggulsterone derivatives as potential anti-austerity agents against PANC-1 human pancreatic cancer cells., Kohyama, Aki, Yokoyama Rei, Dibwe Dya Fita, El-Mekkawy Sahar, Meselhy Meselhy R., Awale Suresh, and Matsuya Yuji , Bioorganic & medicinal chemistry letters, Volume 30, Issue 7, p.126964, (2020) Abstract

E- and Z-guggulsterones and nine guggulsterone derivatives (GSDs) were synthesized and evaluated for their preferential cytotoxicity against human PANC-1 cell in nutrient deprived medium utilizing antiausterity strategy. Among the synthesized compounds, GSD-1 and GSD-7 showed potent cytotoxicity against PANC-1 cells under nutrient-deprived conditions in a concentration dependent manner, with a PC value of 1.6 μM and 3.2 μM, respectively. The effect of GSD-1 and GSD-7 was further evaluated in a real time using live cell imaging. Both of these compounds altered PANC-1 cell morphology, leading to cell death at sub micromolar concentration range. GSD-1 and GSD-7 also inhibited PANC-1 cell colony formation in a concentration-dependent manner. GSD-1 and GSD-7 are lead structure for the anti-austerity drug development.

Sesquiterpenes from Cymbopogon proximus, El-Askary, Hesham I., Meselhy Meselhy R., and Galal Ahmed M. , Molecules, Volume 8, Issue 9, p.670-677, (2003) Abstract
Quinic acid derivatives from Artemisia annua L. leaves; biological activities and seasonal variation, H.I. El-Askary, S.S. Mohamed, El-Gohari H. M. A., Ezzat S. M., and Meselhy M. R. , South African Journal of Botany, Volume 128, p.200-208, (2020)
Preparation of Lignan-Rich Extract from the Aerial Parts of Using Nonconventional Methods., Meselhy, Meselhy R., Abdel-Sattar Ola E., El-Mekkawy Sahar, El-Desoky Ahmed M., Mohamed Shanaz O., Mohsen Sobhy M., Abdel-Sattar Essam, and Halawany Ali El- , Molecules (Basel, Switzerland), Volume 25, Issue 5, (2020) Abstract

Phyllanthin and related lignans were found to be responsible, at least in part, for most of the activity of species. This observation encouraged the authors to develop methods for the preparation of an extract rich in phyllanthin and related lignans from the aerial parts of L. Direct extraction with solvents produced extracts with variable yields and contents of lignans. Lignans were identified by LC-ESI-MS analysis as phyllanthin (used as marker substance), hypophyllanthin, phylltetralin, nirtetralin, and niranthin. Extraction with boiling water produced 18.10 g% (/) extract with a trace amount of lignans (phyllanthin content of 0.33 ± 0.10 mg/g extract), while extraction with MeOH gave 3.6 g% / extract with a low phyllanthin content (3.1 mg/g extract), as determined by HPLC. However, Soxhlet extraction with hexane, CHCl, or acetone gave extracts with low yields (0.82, 1.12, and 3.40 g% /, respectively) and a higher phyllanthin contents (36.2 ± 2.6, 11.7 ± 1.68, and 11.7 ± 1.10 mg/g extract, respectively). Extraction quality and efficiency were optimized by adopting the following three different approaches: (1) Alkaline digestion of the plant material with 30% potassium hydroxide yielded 3.1 g% / of purified extract with high phyllanthin content (22.34 ± 0.13 mg/g); (2) microwave-assisted extraction using 80% MeOH gave an extract with a better yield (8.13 g% /) and phyllanthin content (21.2 ± 1.30 mg/g) (after filtration through a Diaion HP-20 column); and (3) treatment of the ground plant material at 50 °C with two hydrolytic enzymes, cellulase (9 U/g for 12 h) and then, protease (4 U/g up to 72 h) optimized the yield of extract (13.92 g% /) and phyllanthin content (25.9 mg/g extract and total lignans content of 85.87 mg/g extract). In conclusion, the nonconventional methods presented here are superior for optimizing the yield of extract and its lignan contents from the aerial parts of .

Potent anticonvulsant paeonimetabolin-I derivatives obtained by incubation of paeoniflorin and thiol compounds with Lactobacillus brevis, Abdel-Hafez, Atef A., Meselhy Meselhy R., Nakamura Norio, Hattori Masao, WATANABE Hiroshi, MOHAMED Tarek A., MAHFOUZ Nadia M., and EL-GENDY Mahmoud A. , Chemical and pharmaceutical bulletin, Volume 46, Issue 9, p.1486-1487, (1998) Abstract
Polyphenols LC-MS2 profile of Ajwa date fruit (Phoenix dactylifera L.) and their microemulsion: Potential impact on hepatic fibrosis, Nematallah, Khaled A., Ayoub Nahla A., Abdelsattar Essam, Meselhy Meselhy R., Elmazar Mohey M., El-Khatib Ahmed H., Linscheid Michael W., Hathout Rania M., Godugu Kavitha, and Adel Aya , Journal of Functional Foods, Volume 49, p.401-411, (2018) Abstract
Phenolic constituents from Grevillea robusta, Ahmed, Amany S., Nakamura Norio, Meselhy Meselhy R., Makhboul Makhboul A., El-Emary Nasr, and Hattori Masao , Phytochemistry, Volume 53, Issue 1, p.149-154, (2000) Abstract
New paeonilactone-A adducts formed by anaerobic incubation of paeoniflorin with Lactobacillus brevis in the presence of arylthiols, Abdel-Hafez, Atef A., Meselhy Meselhy R., Nakamura Norio, Hattori Masao, EL-GENDY Mahmoud A., MAHFOUZ Nadia M., and MOHAMED Tarek A. , Chemical and pharmaceutical bulletin, Volume 49, Issue 7, p.918-920, (2001) Abstract
Natural Products as Antiviral Agents Natural Products as Antiviral Agents, 1-29, 1992, El-Mekkawy, Sahar, Meselhy Meselhy Ragab, Abdel-Hafez Atef Abdel-Monem, Nakamura Norio, Hattori Masao, Kawahata Takuya, and Otake Toru , Chemical & pharmaceutical bulletin, Volume 50, Issue 4, p.523-529, (2002) Abstract
Metabolism of strychnine N-oxide and brucine N-oxide by human intestinal bacteria, El-Mekkawy, Sahar, Meselhy M. R., Kawata Yukio, KADOTA Shigetoshi, Hattori Masao, and NAMBA Tsuneo , Planta medica, Volume 59, Issue 04, p.347-350, (1993) Abstract
Intestinal injury can be effectively prevented by in gamma irradiated rats., Khayyal, Mohamed T., El-Baz Farouk K., Meselhy Meselhy R., Ali Gamila H., and El-Hazek Rania M. , Heliyon, Volume 5, Issue 5, p.e01814, (2019) Abstract

is one of the most common microalgae that is used as human food. It is isolated from the salty lakes in El-Fayoum and Lake of Bardawil-Sinai in Egypt and can withstand very high concentrations of salt: The potentiality of , a unicellular biflagellate green alga to protect against intestinal injury induced after radiation exposure was studied. was given orally in doses of 100 and 200 mg/kg to male Wistar rats for 5 days before exposure to 6 Gray (Gy) gamma radiation and continued for a further two days. Rats were sacrificed 24 h later and intestinal segments were dissected out. One segment was examined histologically and another was used to prepare homogenates to assess relevant biochemical parameters reflecting intestinal injury. Radiation exposure led to a rise in the histological damage score, an increase in tissue tumor necrosis factor (TNF-α), interleukin (IL-1β) and thiobarbituric acid reactive substances (TBARS) but a reduction in tissue reduced glutathione (GSH) and in serum citrulline. Pretreatment with either dose of effectively reduced the severity of intestinal mucositis induced by gamma radiation.

Inhibitory effects of egyptian folk medicines oh human immunodeficiency virus (HIV) reverse transcriptase, El-Mekkawy, Sahar, Meselhy Meselhy R., KUSUMOTO Ines Tomoco, KADOTA Shigetoshi, Hattori Masao, and NAMBA Tsuneo , Chemical and Pharmaceutical Bulletin, Volume 43, Issue 4, p.641-648, (1995) Abstract
Inhibitory effect of component from Ganoderma lucidum on the growth of human immunodeficiency virus (HIV) and the protease activity, Hattori, Masao, El-Mekkawy S., and Meselhy M. R. , Proceedings of the 1st International Symposium on Ganoderma Lucidum in Japan, Mizuno T, Ide N and Hasegawa Y (eds), p.128-135, (1997) Abstract
Inhibition of cytopathic effect of human immunodeficiency virus type-1 by various phorbol derivatives, El-Mekkawy, Sahar, Meselhy Meselhy Ragab, Abdel-Hafez Atef Abdel-Monem, Nakamura Norio, Hattori Masao, Kawahata Takuya, and Otake Toru , Chemical and pharmaceutical bulletin, Volume 50, Issue 4, p.523-529, (2002) Abstract
Guaianolides from Centaurea scoparia, Helal, Amr M., Nakamura Norio, Meselhy Meselhy R., El-Fishawy Ahlam M., Hattori Masao, and Mahran Gamal H. , Phytochemistry, Volume 45, Issue 3, p.551-554, (1997) Abstract
Evaluation of the Anti-inflammatory and Antioxidant Activities of Selected Resin Exudates, Ali, Dalia E., Abdelrahman Rehab S., Gedaily Rania El A., Ezzat Shahira M., Meselhy Meselhy R., and Abdel-Sattar Essam , Tropical Journal of Natural Product Research, Volume 4, Issue 7, p.255-261, (2020)
Essential oil of cultivated in Egypt: seasonal variation in chemical composition and anticholinesterase activity., Madi, Yasmine F., Choucry Mouchira A., Meselhy Meselhy R., and El-Kashoury El-Sayeda A. , Natural product research, p.1-5, (2020) Abstract

The yield of essential oil obtained by hydrodistillation of fresh leaves ranged from 0.15% to 0.46% w/w; being the highest in spring and the lowest in winter. The oil sample obtained in winter exhibited a moderate acetylcholinesterase inhibitory activity (IC 2.86 ± 0.17 mg/mL), compared to physostigmine (IC 0.012 mg/mL), while other samples were relatively weak (IC values of 2.86-5.40 mg/mL). In all samples, oxygenated monoterpenes were predominating (73.22-89.32%). GC-MS identified a total of 61, 25, 50 and 63 components in oil samples obtained in spring, summer, autumn and winter, respectively. Citral content was the highest in autumn and summer samples (82.02% and 80.01% citral; respectively) and the lowest in winter sample (60.01%). Citral, isolated from the oil demonstrated a relatively potent anticholinesterase activity (IC 0.21 ± 0.01 mg/mL).

Effects of paeoniflorin derivatives on scopolamine-induced amnesia using a passive avoidance task in mice; structure-activity relationship, Abdel-Hafez, Atef A., Meselhy Meselhy R., Nakamura Norio, Hattori Masao, WATANABE Hiroshi, MUKARAMI Yukihisa, EL-GENDY Mahmoud A., MAHFOUZ Nadia M., and MOHAMED Tarek A. , Biological and Pharmaceutical Bulletin, Volume 21, Issue 11, p.1174-1179, (1998) Abstract
Diterpene acids from Conyza incana, Galal, Ahmed M., Abdel-Sattar Essam, El-Feraly Farouk S., Mossa Jaber S., Meselhy Meselhy R., KADOTA Shigetoshi, and NAMBA Tsuneo , Phytochemistry, Volume 48, Issue 1, p.159-163, (1998) Abstract
Developing of anti-HIV agents from natural resources (Chemical & Pharmacological study), Meselhy, Meselhy Ragab, El-Mekkawy Sahar, Ma Chaomei, Nakamura Norio, TEWTRAKUL Supinya, and Hattori Masao , 和漢医薬学雑誌, Volume 22, Issue 1, p.116-128, (2005) Abstract
Comparative Antioxidant Activities of Selected Apiaceous Plants, Emad, Ayat M., Ali Sherifa F., Meselhy Meselhy R., and Sattar Essam A. , Pharmacognosy Journal, Volume 11, Issue 6, p.1-6, (2019)
Anticonvulsant activity of paeonimetabolin-I adducts obtained by incubation of paeoniflorin and thiol compounds with Lactobacillus brevis, Abdel-Hafez, Atef A., Meselhy Meselhy R., Nakamura Norio, Hattori Masao, WATANABE Hiroshi, MURAKAMI Yukihisa, EL-GENDY Mahmoud A., MAHFOUZ Nadia M., and MOHAMED Tarek A. , Biological and Pharmaceutical Bulletin, Volume 22, Issue 5, p.491-497, (1999) Abstract
Anti-inflammatory and antioxidant effects of Apium graveolens L. extracts mitigate against fatal acetaminophen-induced acute liver toxicity., Emad, Ayat M., Ali Sherifa F., Abdel-Rahman Engy A., Meselhy Meselhy R., Farag Mohamed A., Ali Sameh S., and Abdel-Sattar Essam A. , Journal of food biochemistry, p.e13399, (2020) Abstract

In the present work, antioxidant activity, total phenolics (TP), and total flavonoids (TF) contents of aqueous and methanol extracts of celery were determined, in addition to untargeted metabolites profiling its methanol celery root extract (MCRE) via UPLC-MS. Although MCRE exhibited the lowest TPC and TFC levels, it presented the most potential hydroxyl radical quenching effect using electron paramagnetic resonance spin trapping technique. Treatment of Acetaminophen-induced hepatotoxicity (AAH) rats with MCRE lowered serum levels of AST, ALT, ALP, TNF-α, and IL-1β significantly. Additionally, MCRE significantly increased total antioxidant capacity (TAC) and glutathione (GSH) levels relative to AAH rats. Strikingly, Kaplan-Meier survival analysis of all groups revealed a 100% prevention of acetaminophen-induced mortality of rats by MCRE pretreatment (100 mg/kg/day). MCRE prevented AAH-associated severe weight loss and elicited normal behavior in the rescued rats. Our results suggest that pretreatment with MCRE can mitigate against overdosed acetaminophen-induced acute liver failure and warrant further investigations on the potential of postinjury intervention. PRACTICAL APPLICATIONS: Acetaminophen-induced hepatotoxicity (AAH) accounts for alerting numbers of overdose-related acute liver failure and liver transplant cases with increased morbidity and mortality rates. Currently proposed mechanisms implicate mitochondria-mediated oxidative stress and inflammation in the pathogenesis of AAH, which underline current interventions employing antioxidants to combat liver damage by over-dosed acetaminophen. The present work uncovers potent protective effects of some celery extracts (and their fractions) against acetaminophen-induced oxidative stress and inflammation. Treatment of rats with fatal liver injury with methanol extract of celery root significantly reduced secretion of liver enzymes and markedly decreased inflammatory as well as oxidative stress markers in these animals. This, in turn, rescued challenged rats exposed to fatal doses of acetaminophen completely, which establishes methanol extracts of celery roots as effective therapeutic intervention against AAH. The antioxidant capacity of the extracts was determined using EPR technique, and the secondary metabolites related to antioxidant activity were characterized via UPLC-MS.

Anti-HIV-1 phorbol esters from the seeds of Croton tiglium, El-Mekkawy, Sahar, Meselhy Meselhy R., Nakamura Norio, Hattori Masao, Kawahata Takuya, and Otake Toru , Phytochemistry, Volume 53, Issue 4, p.457-464, (2000) Abstract
Anti-HIV-1 and anti-HIV-1-protease substances from Ganoderma lucidum, El-Mekkawy, Sahar, Meselhy Meselhy R., Nakamura Norio, Tezuka Yasuhiro, Hattori Masao, Kakiuchi Nobuko, Shimotohno Kunitada, Kawahata Takuya, and Otake Toru , Phytochemistry, Volume 49, Issue 6, p.1651-1657, (1998) Abstract
12-O-acetylphorbol-13-decanoate potently inhibits cytopathic effects of human immunodeficiency virus type 1 (HIV-1), without activation of protein kinase C, El-Mekkawy, Sahar, Meselhy Meselhy R., Nakamura Norio, Hattori Masao, Kawahata Takuya, and Otake Toru , CHEMICAL AND PHARMACEUTICAL BULLETIN-TOKYO-, Volume 47, p.1346-1347, (1999) Abstract