Multi-target action of Garcinia livingstonei extract and secondary metabolites against fatty acid synthase, α-glucosidase, and xanthine oxidase.

Garcinia livingstonei is a traditional herbal medicine that showed beneficial health effects and bioactivities. Four compounds have been isolated from the plant leaves and were elucidated as lupeol, betulin, podocarpusflavone A, and amentoflavone. The inhibitory activities of G. livingstonei extract and isolated metabolites against fatty acid synthase (FAS), α-glucosidase, and xanthine oxidase (XO) were investigated in vitro. The affinity of the compounds toward the studied enzymes was investigated in silico. The plant extract inhibited FAS, α-glucosidase, and XO with IC50 values of 26.34, 67.88, and 33.05 µg/mL, respectively. Among the isolated metabolites, betulin exhibited the most inhibitory activity against α-glucosidase and XO with IC50 values of 38.96 and 30.94 µg/mL, respectively. Podocarpusflavone A and betulin were the most potent inhibitors of FAS with IC50 values of 24.08 and 27.96 µg/mL, respectively. Computational studies corroborated these results highlighting the interactions between metabolites and the enzymes. In conclusion, G. livingstonei and its constituents possess the potential to modulate enzymes involved in metabolism and oxidative stress.

Dietary Guduchi (Tinospora cordifolia) enhanced the growth performance, antioxidative capacity, immune response and ameliorated stress-related markers induced by hypoxia stress in Nile tilapia (Oreochromis niloticus).

Nile tilapia can tolerate a wide range of farming conditions; however, fluctuations in the environmental conditions may impair their health status. The incorporation of medicinal herbs in aquafeed is suggested to overcome stressful conditions. In this study, dietary Guduchi (Tinospora cordifolia) was evaluated on the growth performance, antioxidative capacity, immune response, and resistance of Nile tilapia against hypoxia stress. Fish fed five diets incorporated with Guduchi at 0, 2, 4, 6, and 8 g/kg for 56 days then exposed with hypoxia stress for 72 h. The growth performance, feed intake, and feed efficiency ratio were significantly (P < 0.05) increased by including Guduchi in tilapia diets regardless of the inclusion level. Similarly, the lipase and protease activities were markedly (P < 0.05) increased in tilapia fed dietary Guduchi. The activities of lysozyme and bactericidal activities in serum and mucus, nitro-blue tetrazolium (NBT), and alternative complement activity (ACH50) were markedly (P < 0.05) enhanced in tilapia treated with Guduchi supplements regardless of the dose. Additionally, the activities of liver and intestinal superoxide dismutase, catalase, and glutathione peroxidase were markedly enhanced (P < 0.05) by including Guduchi in tilapia diets compared with the control. Before and after hypoxia stress, tilapia-fed dietary Guduchi had lower glucose and cortisol levels than fish-fed Guduchi-free diets (P < 0.05). In all groups, glucose and cortisol levels were markedly higher after hypoxia compared before hypoxia stress (P < 0.05). In conclusion, dietary Guduchi can be included at 5.17-5.49 g/kg to enhance the growth performance, digestive enzyme activity, immune and antioxidative responses, and the resistance of Nile tilapia against hypoxia stress.

Development of potential anticancer agents and apoptotic inducers based on 4-aryl-4H chromene scaffold: Design, synthesis, biological evaluation and insight on their proliferation inhibition mechanism.

An array of 4-aryl-2-amino-4H chromene derivatives were designed, synthesized, and evaluated for cytotoxic activity against four cancer cell lines and two non-cancerous cell lines. The most active candidates were further screened for their in vitro anticancer activity on NCI panel of 60 human cancer cell lines where compounds 2a, 2b, 4a-2, and 2e showed promising activity against various leukemia, non-small lung, renal, prostate, and breast cancer cell lines, particularly against NCI-H522 non-small lung cancer cell line (GI50 of 0.35-0.60 µM), MCF7 breast cancer cell line (GI50 of 0.34-0.59 µM), and MDA-MB-468 breast cancer cell line (GI50 of 0.23-0.40 µM). Compound 2b was the most potent against all leukemia and prostate cancer cell lines with GI50 values (0.29-0.60 µM). Compound 2b inhibited the proliferation of MCF-7 and HepG2 cells by inducing cell cycle arrest and apopotosis. 2b downregulated the mRNA abundance of BAX, Apaf-1 and caspase-3 and upregulated BCL-2. The activities of caspase-3 and caspase-9 were declined in MCF-7 and HepG2 cells treated with compound 2b. Compounds 2b and 4a-2 inhibited tubulin polymerization, with an IC50 values of 0.92 and 1.13 µM, respectively. These findings indicate that these synthesized compounds may represent potential drug candidates to inhibit the proliferation of different types of cancer cells.

Ginseng® as a reproductive enhancer agent for African catfish, Clarias gariepinus (Burchell, 1822).

Ginseng (Ge) is one of the most famous and precious consumed herbal medicines around the world. Ge plant roots have many advantages regarded as important in increasing fish production. Thus, the present study was conducted to investigate the possibility of using different levels (0.0, 100, and 200 mg/kg diet) of Ge as a reproductive enhancer agent for African catfish, Clarias gariepinus males. Results revealed that fish fed 200 mg Ge/kg diet significantly (P ˂ 0.05) increased growth performance, feed efficiency, gonado-somatic index, hematological parameters, serum follicle-stimulating hormone, total antioxidant capacity, sperm quality parameters, and ultrastructure of spermatozoa, as well as led to positively improved of the histological structure of the testes tissue compared to other treatments. Based on the obtained findings, it could be concluded that the effective use of dietary Ge at a level of 200 mg/kg as a promising reproductive agent for adult African catfish males consequently led to the sustainability of aquaculture for African catfish.

Prognostic Value of Tumor Associated Macrophage Markers CD163 and CD68 Immunohistochemistry in Classical Hodgkin Lymphoma.

BACKGROUND: Tumor associated macrophages have been implicated in the pathogenesis of classical Hodgkin's lymphoma and have been suggested to have a negative impact on outcome. The aim of this study is to determine the expression and the prognostic impact of CD163 and CD68 markers of the tumor associated macrophages, in the initial positively infiltrated bone marrow biopsy specimens of our subjects by immunohistochemistry and to corre¬late their expression with other clinical and laboratory prognostic factors. METHODS: This study was conducted on fifty-one patients with de novo classical Hodgkin's lymphoma, presenting to the Clinical Pathology Department at the National Cancer Institute, Cairo University. CD163 and CD68 were detected in the initial bone marrow biopsy specimens from our subjects by immunohistochemistry. RESULTS: The present study included 51 patients with CHL. They comprised 24 males (47.1%) and 27 females (52.9%) with an age of 32.9 ± 14.5 years. After treatment, 33 patients (64.7%) achieved complete remission while 18 patients (35.3%) failed. Comparison between patients with CR and patients without revealed significantly lower CD68 expression [median (IQR): 30.0 (15.0 - 47.5%) versus 55.0 (43.8 - 55.0%), p = 0.003] and CD163 expression [25.0 (10.0 - 37.5%) versus 45.0 (0.35 - 55.0%)] in CR patients. Binary logistic regression analysis identified CD68 and CD163 expressions as significant predictors of CR in univariate and multivariate analyses. CONCLUSIONS: The expressions of both tumor-associated markers, CD68 and CD163, are significant predictors of CR in patients with CHL.

Assessing the effectiveness of CoQ10 dietary supplementation on growth performance, digestive enzymes, blood health, immune response, and oxidative-related genes expression of Nile tilapia (Oreochromis niloticus).

The present study was conducted to investigate the effects of CoQ10 dietary supplementation on growth performance, feed utilization, blood profile, immune response, and oxidative status of Nile tilapia (12.4 ± 0.11 g, initial body weight). Five experimental diets were formulated containing CoQ10 at levels of 0, 10, 20, 30, 40 mg kg-1 diet (D1, D2, D3, D4, and D5, respectively). The results of a 56-days feeding trial showed that, significantly higher weight gain % (WG %), specific growth rate (SGR), feed intake (FI), and feed efficiency ratio (FER) were recorded in fish groups fed diets supplemented with different levels of CoQ10 than fish fed the control diet, while survival rate (SR%), condition factor (CF), hepatosomatic index (HSI) and viscerasomatic index (VSI) showed no obvious differences (P > 0.05) among all experimental groups. The highest activities of digestive enzymes (protease, amylase, and lipase) were recorded in D3, D4, and D5 groups. Moreover, blood status of all experimental fish was within normal rates and significant alterations were only in the case of glucose, cortisol, total cholesterol (T-Chol), triglycerides, and total protein (TP), where fish fed on D3, D4 and D5 diets exhibited lower values of glucose, cortisol, T-Chol, and triglycerides and higher values of TP. Furthermore, the lowest values of immune response [lysozyme, bactericidal, respiratory burst (NBT), and alternative complement pathway activities (ACP)], antioxidant capacity and oxidative related genes expressions [superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX)] resulted from feeding on the basal diet (D1) compared to CoQ10 diets, especially with its high levels {≥20 mg kg-1 diet (D3, D4, and D5)} in most cases. In conclusion, our results suggest that the use of ≥20 mg CoQ10 kg-1 diet improves the growth and health being of Nile tilapia.

A multicomponent reaction to design antimalarial pyridyl-indole derivatives: Synthesis, biological activities and molecular docking.

Using fragment-based design strategy, new pyridyl-indole hybrids 4a-y and indole intermediates 3a-e were synthesized using multicomponent one pot reaction. The synthesized compounds were subjected to screening for antimalarial activity against chloroquine sensitive (D6) and chloroquine resistant (W2) strains of Plasmodium falciparum. Several compounds exhibited antimalarial activity with IC50 values in the range of 1.47-9.23 µM, and 1.16-7.66 µM, for D6 and W2 strains, respectively. Compounds 4a, 4k and 4u showed the highest selectivity index among all the tested compounds (S.I. ranged 3.8-10). Binding interactions between the active antimalarial compounds and the active site of quadruple mutant Plasmodium falciparum dihydrofolate reductase enzyme have been investigated using molecular docking analysis.

OUTER RETINAL LAYER THICKNESS AS GOOD VISUAL PREDICTOR IN PATIENTS WITH DIABETIC MACULAR EDEMA.

PURPOSE: To evaluate the relationship between outer retinal layer (ORL) thickness in diabetic macular edema to visual acuity (VA). METHODS: Ninety-five eyes were included in this prospective nonrandomized case-control study. They divided into 30 cases of healthy normal subjects and 65 cases of nonproliferative diabetic retinopathy with diabetic macular edema. Complete ophthalmic examination and spectral domain-optical coherence tomography were done for all cases and analyzed to measure central foveal point thickness (CFT), ORL thickness at fovea, and subfoveal choroidal thickness. RESULTS: The ORL thickness was significantly thinner in diabetic macular edema group (85.3 µm) than controls (99.9 µm) (P = 0.002). There was higher significant correlation between ORL thickness and logMAR VA (r = -0.87, P < 0.001) than correlation between CFT and VA (r = 0.18, P = 0.16). The cutoff point of the relationship between ORL thickness and VA was 88 µm with moderate sensitivity (81%) and high specificity (88%), below which vision is affected. Outer retinal layer thickness is significantly related to subfoveal choroidal thickness but not CFT. CONCLUSION: This study revealed reduction in ORL thickness in diabetic macular edema. There is a higher and stronger correlation between ORL thickness and vision than that between CFT and vision.

Epigenetic Modifiers Induce Bioactive Phenolic Metabolites in the Marine-Derived Fungus Penicillium brevicompactum.

Fungi usually contain gene clusters that are silent or cryptic under normal laboratory culture conditions. These cryptic genes could be expressed for a wide variety of bioactive compounds. One of the recent approaches to induce production of such cryptic fungal metabolites is to use histone deacetylases (HDACs) inhibitors. In the present study, the cultures of the marine-derived fungus Penicillium brevicompactum treated with nicotinamide and sodium butyrate were found to produce a lot of phenolic compounds. Nicotinamide treatment resulted in the isolation and identification of nine compounds 1⁻9. Sodium butyrate also enhanced the productivity of anthranilic acid (10) and ergosterol peroxide (11). The antioxidant as well as the antiproliferative activities of each metabolite were determined. Syringic acid (4), sinapic acid (5), and acetosyringone (6) exhibited potent in vitro free radical scavenging, (IC50 20 to 30 µg/mL) and antiproliferative activities (IC50 1.14 to 1.71 µM) against HepG2 cancer cell line. Furthermore, a pharmacophore model of the active compounds was generated to build up a structure-activity relationship.

Design and synthesis of new coumarin hybrids and insight into their mode of antiproliferative action.

Molecular hybridization approach was used to synthesize three series of coumarin based hybrids by conglomerate a substituted chalcones, acrylohydrazides, and pyridines moieties with 8-methoxy coumarin. The hybrids showed significant cytotoxic activity against liver cancer Hep G2 and Leukemia K562 cell lines with IC50 values 0.49-3.96µM, comparable to the positive controls and exhibited weak activity against the normal cell line WI-38, thus indicating selectivity toward the tumor cells. Coumarin-chalcone hybrids 2a-c have demonstrated the most promising activity against both cancer cell lines with IC50 values of 0.65-2.02µM. Interestingly, the acrylohydrazide hybrid 4c showed the highest cytotoxic activity against the leukemia cell line (K562) with IC50 value of 0.49µM. All the investigated coumarin hybrids were able to increase the caspase-3 and caspase-9 proteins level expression relative to that of the untreated cells suggesting that coumarin hybrids-induced apoptosis was, in part, due to activation of caspases 3 and 9. Apoptosis was further confirmed with down-regulation of Bcl-2 and up-regulation of Bax protein expression level. Furthermore, cell cycle analysis of 2a and 4c showed apoptotic signals activation, as a consequence of arrest in G2/M phase. Results of our study can shed light on coumarin-based hybrids as promising anticancer leads.

Diversity-oriented natural product platform identifies plant constituents targeting Plasmodium falciparum.

BACKGROUND: A diverse library of pre-fractionated plant extracts, generated by an automated high-throughput system, was tested using an in vitro anti-malarial screening platform to identify known or new natural products for lead development. The platform identifies hits on the basis of in vitro growth inhibition of Plasmodium falciparum and counter-screens for cytotoxicity to human foreskin fibroblast or embryonic kidney cell lines. The physical library was supplemented by early-stage collection of analytical data for each fraction to aid rapid identification of the active components within each screening hit. RESULTS: A total of 16,177 fractions from 1300 plants were screened, identifying several P. falciparum inhibitory fractions from 35 plants. Although individual fractions were screened for bioactivity to ensure adequate signal in the analytical characterizations, fractions containing less than 2.0 mg of dry weight were combined to produce combined fractions (COMBIs). Fractions of active COMBIs had EC50 values of 0.21-50.28 and 0.08-20.04 µg/mL against chloroquine-sensitive and -resistant strains, respectively. In Berberis thunbergii, eight known alkaloids were dereplicated quickly from its COMBIs, but berberine was the most-active constituent against P. falciparum. The triterpenoids α-betulinic acid and ß-betulinic acid of Eugenia rigida were also isolated as hits. Validation of the anti-malarial discovery platform was confirmed by these scaled isolations from B. thunbergii and E. rigida. CONCLUSIONS: These results demonstrate the value of curating and exploring a library of natural products for small molecule drug discovery. Attention given to the diversity of plant species represented in the library, focus on practical analytical data collection, and the use of counter-screens all facilitate the identification of anti-malarial compounds for lead development or new tools for chemical biology.

Bioactive Formylated Flavonoids from Eugenia rigida: Isolation, Synthesis, and X-ray Crystallography.

Two new flavonoids, rac-6-formyl-5,7-dihydroxyflavanone (1) and 2',6'-dihydroxy-4'-methoxy-3'-methylchalcone (2), together with five known derivatives, rac-8-formyl-5,7-dihydroxyflavanone (3), 4',6'-dihydroxy-2'-methoxy-3'-methyldihydrochalcone (4), rac-7-hydroxy-5-methoxy-6-methylflavanone (5), 3'-formyl-2',4',6'-trihydroxy-5'-methyldihydrochalcone (6), and 3'-formyl-2',4',6'-trihydroxydihydrochalcone (7), were isolated from the leaves of Eugenia rigida. The individual (S)- and (R)-enantiomers of 1 and 3, together with the corresponding formylated flavones 8 (6-formyl-5,7-dihydroxyflavone) and 9 (8-formyl-5,7-dihydroxyflavone), as well as 2',4',6'-trihydroxychalcone (10), 3'-formyl-2',4',6'-trihydroxychalcone (11), and the corresponding 3'-formyl-2',4',6'-trihydroxydihydrochalcone (7) and 2',4',6'-trihydroxydihydrochalcone (12), were synthesized. The structures of the isolated and synthetic compounds were established via NMR, HRESIMS, and electronic circular dichroism data. In addition, the structures of 3, 5, and 8 were confirmed by single-crystal X-ray diffraction crystallography. The isolated and synthetic flavonoids were evaluated for their antimicrobial and cytotoxic activities against a panel of microorganisms and solid tumor cell lines.

New insights into the anti-inflammatory and anti-melanoma mechanisms of action of azelaic acid and other Fusarium solani metabolites via in vitro and in silico studies.

Metabolites exploration of the ethyl acetate extract of Fusarium solani culture broth that was isolated from Euphorbia tirucalli root afforded five compounds; 4-hydroxybenzaldehyde (1), 4-hydroxybenzoic acid (2), tyrosol (3), azelaic acid (4), malic acid (5), and fusaric acid (6). Fungal extract as well as its metabolites were evaluated for their anti-inflammatory and anti-hyperpigmentation potential via in vitro cyclooxygenases and tyrosinase inhibition assays, respectively. Azelaic acid (4) exhibited powerful and selective COX-2 inhibition followed by fusaric acid (6) with IC50 values (2.21 ± 0.06 and 4.81 ± 0.14 µM, respectively). As well, azelaic acid (4) had the most impressive tyrosinase inhibitory effect with IC50 value of 8.75 ± 0.18 µM compared to kojic acid (IC50 = 9.27 ± 0.19 µM). Exclusive computational studies of azelaic acid and fusaric acid with COX-2 were in good accord with the in vitro results. Interestingly, this is the first time to investigate and report the potential of compounds 3-6 to inhibit cyclooxygenase enzymes. One of the most invasive forms of skin cancer is melanoma, a molecular docking study using a set of enzymes related to melanoma suggested pirin to be therapeutic target for azelaic acid and fusaric acid as a plausible mechanism for their anti-melanoma activity.

Cytotoxicity and modulation of cancer-related signaling by (Z)- and (E)-3,4,3',5'-tetramethoxystilbene isolated from Eugenia rigida.

Bioassay-guided fractionation of the leaves of Eugenia rigida yielded three stilbenes, (Z)-3,4,3',5'-tetramethoxystilbene (1), (E)-3,4,3',5'-tetramethoxystilbene (2), and (E)-3,5,4'-trimethoxystilbene (3). Their structures were determined using 1D- and 2D-NMR spectroscopy and HRESIMS. The sterically hindered Z-stereoisomer 1, a new natural product, was prepared by time-dependent photoisomerization of the E-isomer (2) under UV irradiation at λ254 nm, while 2,3,5,7-tetramethoxyphenanthrene (5) was identified at λ365 nm by UHPLC/APCI-MS and NMR spectroscopy. Compounds 1-3 were tested against a panel of luciferase reporter gene assays that assess the activity of many cancer-related signaling pathways, and the Z-isomer (1) was found to be more potent than the E-isomer (2) in inhibiting the activation of Stat3, Smad3/4, myc, Ets, Notch, and Wnt signaling, with IC50 values between 40 and 80 µM. However, both compounds showed similar inhibition against Ap-1 and NF-κB signaling. In addition, 1 demonstrated cytotoxic activity toward human leukemia cells, solid tumor cells of epidermal, breast, and cervical carcinomas, and skin melanoma, with IC50 values between 3.6 and 4.3 µM, while 2 was weakly active against leukemia, cervical carcinoma, and skin melanoma cells. Interestingly, 2 showed antioxidant activity by inhibition of ROS generation to 50% at 33.3 µM in PMA-induced HL-60 cells, while 1 was inactive at 100 µM (vs Trolox 1.4 µM).

Adrenal Insufficiency Secondary to Monkeypox Infection: A Case Report.

Our case report confirms adrenal insufficiency following three weeks of monkeypox infection in an immunocompetent patient. As there is no specific treatment for monkeypox, steroid replacement therapy remains the cornerstone of managing adrenal insufficiency. By highlighting the importance of early identification and tracing in our case report, we contribute to the growing body of knowledge on monkeypox and emphasize the importance of identifying adrenal insufficiency and other complications like meningoencephalitis, prompting a significant early intervention that can help manage these complications effectively, potentially improving patient outcomes. In addition, understanding disease progression by tracing monkeypox cases provides valuable information on the disease's natural history, including the timeline and sequence of symptoms, associated complications, and outcomes, to avoid any small chance related to our lack of validated knowledge or incorrect assessment of the disease or the associated complications between an exposure and an effect in the target organs.

Screening and Risk Factors for Retinopathy of Prematurity in a Tertiary Care Hospital in Cairo, Egypt.

Purpose: To evaluate the retinopathy of prematurity (ROP) prevalence, risk factors and screening outcome in a tertiary hospital in Cairo, Egypt. Methods: A prospective observational study was done in Neonatal Intensive Care Unit in Ain Shams University Hospital. A total of 159 premature infants were screened for ROP based on the most inclusive criteria reported to date. Screening included premature infants with gestational age (GA) of ≤34 weeks or birth weight (BW) of ≤2000 grams, or GA >34 weeks or BW >2000 grams, with multiple co-morbidities. The prevalence of ROP, plus disease and their correlation with risk factors of interest were studied. Results: The GA of the included infants ranged from 27 to 36 weeks, mean (SD) 31.87 (± 1.81) weeks. The BW ranged from 640 to 3900 grams, mean (SD) 1784.71 (± 560.30) grams. The prevalence of ROP more than stage 0 was 25.8% (41 infants), 7.3% of the cases (11 infants) showed plus disease and 6.3% (10 infants) showed severe ROP requiring treatment. Of those, 2 cases (20%) fell outside the British Guideline's criteria for Screening. There was a highly significant (p < 0.0001) correlation between ROP more than stage 0 and low GA, low BW, mechanical ventilation, respiratory distress syndrome, necrotizing enterocolitis, intraventricular haemorrhage, and blood transfusion. No significant correlation was found between appearance of ROP more than stage 0 and gender (p = 0.911), patent ductus arteriosus (p =0.187), or sepsis (p =0.998). Conclusion: ROP is a significant problem in the premature infants in Egypt. Extremely premature infants with lower BW are more prone to develop ROP. However, cases with higher GA and BW than mentioned in the British guidelines screening criteria especially with multiple comorbidities showed severe ROP requiring intervention, which implies the need to develop a screening guideline for the Egyptian population.

Characterization of Possible α-Glucosidase Inhibitors from Trigonella stellata Extract Using LC-MS and In Silico Molecular Docking.

The current study accentuates the significance of performing the multiplex approach of LC-HRESIMS, biological activity, and docking studies in drug discovery, taking into consideration a review of the literature. In this regard, the investigation of antioxidant and cytotoxic activities of Trigonella stellata collected from the Egyptian desert revealed a significant antioxidant capacity using DPPH with IC50 = 656.9 µg/mL and a moderate cytotoxicity against HepG2, MCF7, and CACO2, with IC50 values of 53.3, 48.3, and 55.8 µg/mL, respectively. The evaluation of total phenolic and flavonoid contents resulted in 32.8 mg GAE/g calculated as gallic acid equivalent and 5.6 mg RE/g calculated as rutin equivalent, respectively. Chemical profiling of T. stellata extract, using LC-HRESIMS analysis, revealed the presence of 15 metabolites, among which eleven compounds were detected for the first time in this species. Interestingly, in vitro testing of the antidiabetic activity of the alcoholic extract noted an α-glucosidase enzyme inhibitory activity (IC50 = 559.4 µg/mL) better than that of the standard Acarbose (IC50 = 799.9 µg/mL), in addition to a moderate inhibition of the α-amylase enzyme (IC50 = 0.77 µg/mL) compared to Acarbose (IC50 = 0.21 µg/mL). α-Glucosidase inhibition was also virtualized by binding interactions through the molecular docking study, presenting a high binding activity of six flavonoid glycosides, as well as the diterpenoid compound graecumoside A and the alkaloid fenugreekine. Taken together, the conglomeration of LC-HRESIMS, antidiabetic activity, and molecular docking studies shed light on T. stellata as a promising antidiabetic herb.

Antitrypanosomal activity of new semi-synthetic bergenin derivatives.

Bergenin and 11-O-(4'-O-methyl galloyl)-bergenin, previously isolated from Crassula capitella extract, were used as starting materials for the synthesis of eight derivatives; four derivatives 2a-2d were synthesized from bergenin through the formation of ester derivatives and four alkyl derivatives 4a-4d were synthesized from 11-O-(4'-O-methyl galloyl)-bergenin. The structures of the synthesized analogues were confirmed upon 1 H and 13 C NMR spectroscopic elucidation. Antileishmanial and antitrypanosomal activities of the synthesized derivatives were evaluated, compounds 11-O-(3',5' di-benzyl, 4'-O-methyl galloyl)-8,10-di-O-benzyl-bergenin (4c) and 11-O-(3',5'di-4-chlorobenzyl,4'-O-methyl galloyl)-8,10di-O-4-chlorobenzyl bergenin (4d) showed potent antitrypanosomal activity with IC50 values of 0.52 and 0.5 µM, respectively and IC90  values of 0.66 µM against T. brucei compared with IC50 and IC90 values of 21.7 and 50.3 µM for the positive control difluoromethylornithine.

Four new phenolics and antiparasitic secondary metabolites from Flacourtia rukam Zoll. & Mortizi.

Phytochemical investigation of Flacourtia rukam Zoll. & Mortizi (F. rukam) leaves and bark led to the isolation and characterization of seventeen compounds of which four phenolics were not previously described; 2-[(benzoyloxy)methyl]-phenyl-O-ß-xylosyl-(1→2)-ß-glucopyranoside (1), 2-[(benzoyloxy)methyl]-4-hydroxyphenyl-O-ß-xylosyl-(1→2)-ß-D-glucopyranoside (2), 2-hydroxy-5-(2-hydroxyphenoxy)phenoxy-ß-glucopyranoside (3) and biphenyl-1,1',2,2'-tetraol (5). Interestingly, the later compound is known as a synthetic but this is the first report for its isolation from nature. Chemical structures were established using extensive analysis of spectroscopic data (1 D and 2 D NMR and HRESIMS). Biphenyl-1,1,2,2'-tetrol (5) exhibited a good activity against Trypanosoma brucei trypomastigotes with IC50= 6.66 ug/mL. Compounds 2, 5, 9, 10, 11 and 12 showed a good in-vitro anti-inflammatory activity using proteinase inhibitory assay. On the contrary, all tested compounds were inactive as antileishmanial or antimalarial.

¹H-NMR Metabolic Profiling, Antioxidant Activity, and Docking Study of Common Medicinal Plant-Derived Honey.

The purpose of this investigation was to determine ¹H-NMR profiling and antioxidant activity of the most common types of honey, namely, citrus honey (HC1) (Morcott tangerine L. and Jaffa orange L.), marjoram honey (HM1) (Origanum majorana L.), and clover honey (HT1) (Trifolium alexandrinum L.), compared to their secondary metabolites (HC2, HM2, HT2, respectively). By using a ¹H-NMR-based metabolomic technique, PCA, and PLS-DA multivariate analysis, we found that HC2, HM2, HC1, and HM1 were clustered together. However, HT1 and HT2 were quite far from these and each other. This indicated that HC1, HM1, HC2, and HM2 have similar chemical compositions, while HT1 and HT2 were unique in their chemical profiles. Antioxidation potentials were determined colorimetrically for scavenging activities against DPPH, ABTS, ORAC, 5-LOX, and metal chelating activity in all honey extract samples and their secondary metabolites. Our results revealed that HC2 and HM2 possessed more antioxidant activities than HT2 in vitro. HC2 demonstrated the highest antioxidant effect in all assays, followed by HM2 (DPPH assay: IC50 2.91, 10.7 µg/mL; ABTS assay: 431.2, 210.24 at 50 ug/mL Trolox equivalent; ORAC assay: 259.5, 234.8 at 50 ug/mL Trolox equivalent; 5-LOX screening assay/IC50: 2.293, 6.136 ug/mL; and metal chelating activity at 50 ug/mL: 73.34526%, 63.75881% inhibition). We suggest that the presence of some secondary metabolites in HC and HM, such as hesperetin, linalool, and caffeic acid, increased the antioxidant activity in citrus and marjoram compared to clover honey.