Mahmoud H. Mohamed

The biochemical and morphological alterations following administration of melatonin, retinoic acid and Nigella sativa in mammary carcinoma: an animal model

Worldwide, breast cancer is the second leading cause of cancer death among women and the third most common cancer. Although our understanding of the molecular basis of this fatal disease has improved, this malignancy remains elusive. Melatonin (Mel), retinoic acid (RA) and Nigella sativa (NS) are substances with anticancer effects. To date, our understanding of the mechanisms of therapeutic effects of these products in mammary cancer is still marginal. To look at the preventive and therapeutic values of these products, we carried out this investigation. An animal model formed of 80 rats was established. The animals were divided into eight groups of 10 animals each: (a) control group injected with the same vehicle used for treatments in the relevant dosages and routes; (b) carcinogen group injected with the known carcinogenic substance 7,12‐di‐methylbenz(a)anthracene (DMBA) that induces mammary carcinoma; (c) three prophylactic (Pro) groups (Mel‐Pro, RA‐Pro and NS‐Pro) injected with test substances (Mel, RA and NS, respectively) 14 days before the intake of the carcinogenic substance DMBA and then continued until the end of the experiments; and (d) three treated (Tr) groups (Mel‐Tr, RA‐Tr and NS‐Tr) injected with the vehicles after the intake of DMBA. In both the Pro and Tr groups, the drugs were daily administered for 3 months. The animals were killed, and their serum and tissues were evaluated for (a) markers of tumorigenicity [serum levels of total sialic acid (TSA) and lipid‐bound sialic acid (LSA)], (b) markers of endocrine derangement (serum prolactin, estradiol and progesterone levels), (c) apoptotic changes [serum tumour necrosis factor (TNF)‐α, tissue caspase‐3 activity, percentage of DNA fragmentation and ultrastructural features of apoptosis] and (d) markers of oxidative stress (tissue levels of lipid peroxides and nitric oxide). Carcinoma was absent both in the control and in the NS‐Pro groups. Mammary carcinoma occurred in DMBA and other Pro and Tr groups. The frequency of mammary carcinoma was high in the carcinogen DMBA group (60%), followed by the Tr (56%) and finally the Pro groups (33%). These tumours included papillary, comedo and cribriform carcinomas. As compared with the control group, the development of carcinoma in the carcinogen DMBA group was associated with increased levels of (a) markers of tumorigenicity (77.0 ± 3.3 vs. 209.0 ± 5.6 and P < 0.05 for TSA; 28.7 ± 1.7 vs. 41.8 ± 1.2 and P < 0.01 for LSA), (b) markers of endocrine derangement (2.5 ± 0.1 vs. 3.6 ± 0.3 and P < 0.05 for prolactin; 39.6 ± 1.3 vs. 24.8 ± 2.1 and P < 0.01 for progesterone and 31.0 ± 0.7 vs. 51.1 ± 3.4 and P < 0.01 for estradiol) and (c) markers of oxidative stress (2.3 ± 0.2 vs. 5.2 ± 0.7 and P < 0.01 for lipid peroxides and 4.4 ± 0.2 vs. 7.6 ± 0.8 and P < 0.01 for nitric oxide). Also, it was associated with decreased levels of markers of apoptotic activity (20.8 ± 1.1 vs. 13.4 ± 0.7 and P < 0.01 for caspase‐3; 29.0 ± 1.7 vs. 20.9 ± 1.3 and P < 0.05 for percentage of DNA fragmentation; and 9.4 ± 0.8 vs. 52.1 ± 3.3 and P < 0.01 for TNF‐α). When compared with the carcinogen DMBA group, the development of carcinoma in the Pro and Tr groups was associated with decreased levels of (a) markers of tumorigenicity, (b) markers of endocrine derangement and (c) markers of oxidative stress. Alternatively, carcinogenicity was associated with statistically significant (P < 0.01) increased levels of markers of apoptotic activity. To conclude, the administration of Mel, RA and NS reduced the carcinogenic effects of DMBA, suggesting a protective role. The possible underlying mechanisms of these effects await further investigations.

A new steroid glycoside and furochromones from Cyperus rotundus L.

Further phytochemical investigation of the aerial parts of Cyperus rotundus L. afforded a new steroid glycoside named sitosteryl (6′-hentriacontanoyl)-β-D-galactopyranoside (4) in addition to three furochromones, khellin (2), visnagin (3) and ammiol (9). Furthermore, benzo-α-pyrone (coumarin) (1), salicylic acid (5), caffeic acid (6), protocatechuic acid (7), p-coumaric acid (8), tricin (10) and isorhamnetin (11) were isolated. The structures of these compounds were established by spectroscopic methods. The isolated furochromones were tested for insect antifeedant activity against larvae Spodoptera littoralis when incorporated in artificial diet and offered to larvae in a chronic feeding bioassay. Also, visnagin, khellin and sitosteryl (6′-hentriacontanoyl)-β-D-galactopyranoside showed strong cytotoxic activity against L5178y mouse lymphoma cells and were also active in the brine shrimp lethality test.

Monoterpene and pregnane glucosides from Solenostemma argel.

From the aerial parts of Solenostemma argel, two monoterpene glucosides have been isolated and identified as 6,7-dihydroxy-dihydrolinalool 3-O-beta-glucopyranoside and 6,7-dihydroxy-dihydrolinalool 7-O-beta-glucopyranoside. A pregnane glucoside was also isolated and assigned as pregn-5-ene-3,14-beta-dihydroxy-7,20-dione 3-O-beta-glucopyranoside together with the known compounds benzyl alcohol O-beta-apiofuranosyl-(1-->6)-beta-glucopyranoside, 2-phenylethyl O-alpha-arabinopyranosyl-(1-->6)-beta-glucopyranoside, astragalin and kaempferol-3-O-alpha-rhamnopyranosyl-(1-->2)-beta-glucopyranoside.

Fructose-amino acid conjugate and other constituents from Cyperus rotundus L.

Further phytochemical study on the aerial parts of Cyperus rotundus L. led to the isolation of a fructose-amino acid conjugate, N-(1-deoxy-α-D-fructos-1-yl)-L-tryptophan (16) and its tautomers, in addition to n-butyl-β-D-fructopyranoside (1), ethyl-α-D-glucopyranoside (2), adenosine (3), (−)-(E)-caffeoylmalic acid (4), vitexin (5), isovitexin (6), orientin (7), epiorientin (8), myricetin 3-O-β-D-galactopyranoside (9), luteolin 7-O-β-D-glucuronopyranoside-6″-methyl ester (10), chlorogenic acid (11), luteolin 4′-O-β-D-glucuronopyranoside (12), luteolin 7-O-β-D-glucuronopyranoside (13), uridine (14) and ellagic acid (15). Their structures were elucidated on the basis of spectroscopic methods. Additionally, antioxidant and α-amylase inhibitory activities of some of the isolated phenolic compounds were carried out.

Megastigmane glycosides from seeds of Trifoliumalexandrinum

Abstract Five megastigmane glycosides have been isolated from the seeds of Trifoliumalexandrinum L., of which two are known compounds, while three are new compounds showingthe presence of apiofuranosyl- (1→2)-glucopyranosyl residue as a sugar moiety. The structures ofthe isolated compounds were established on the basis of NMR and mass spectral data.

19F NMR spectrometric determination of the partition coefficients of some fluorinated psychotropic drugs between phosphatidylcholine bilayer vesicles and water

A simple 19F NMR spectrometric method was proposed for the determination of the partition coefficients of fluorinated psychotropic drugs, trifluoperazine (TFPZ), flunitrazepam (FNZ) and flurazepam (FZ) between phosphatidylcholine (PC) bilayer of small unilamellar vesicles (SUVs) and water (buffer). Each 19F NMR spectrum of these drugs in the presence of PC SUV showed a single signal accompanying a PC concentration-depending shift change and broadening, which indicated a fast exchange of these drugs between the water phase and the PC bilayer of SUV. From the relationship between the 19F chemical shift change (Deltadelta) of each drug and the PC concentration, the molar partition coefficients (K(p)s) were calculated and obtained with a good precision of RSD below 6%. The fractions of the partitioned drugs calculated by using the obtained K(p)-values were in a good agreement with the experimental values. The results demonstrate that the 19F NMR method can be usefully applied to the determination of partition coefficients of many drugs having fluorine atom(s) without any separation procedure, especially for drugs which do not have absorption in the ultraviolet or visible region, or those having absorption but show insignificant spectral changes according to their incorporation to PC bilayers (e.g. FNZ).

Phenylpropanoid glycosides ofPrunus ssiori

Abstract Two new bitter phenylpropanoid glucosides, 2-(3,4-methylenedioxyphenyl)-ethyl-(6-O-caffeoyl)- β- d -glucopyranoside and 3-O-caffeoyl-β- d -fructofuranosyl, 2,3,4,6-tetra-O-acetyl- α- d -glucopyranoside, have been isolated together with the known compounds, 6-O-caffeoyl- d -glucopyranoside and 2-(3,4-dihydroxyphenyl)-ethyl-(6-O-caffeoyl)-β- d -glucopyranoside, from the bark ofPrunus ssiori. The structures of the isolated compounds have been established by extensive spectroscopic studies.

Alkaloids from seeds of Lupinus varius and L. hartwegii

Abstract A new lupin alkaloid, (−)-13 β -hydroxymultiflorine, was isolated from an ethanol extract of the seeds of Lupinus varius , together with 13 known lupin alkaloids. In addition, two new lupin alkaloids, (+)-2 β -hydroxyaphylline and (+)-13 α -hydroxyaphyllidine, were isolated from seeds of L. hartwegii , together with another 11 known lupin alkaloids. The identification of all compounds was established by spectral analysis.

(+)-15β-Hydroxy-17-oxolupanine a lupin alkaloid from the seeds ofLupinus albus

Abstract A new lupin alkaloid (+)-15β-hydroxy-17-oxolupanine was isolated from the ethanol extract of the seeds of Lupinus albus together with (+)-tetrahy

Peculiar side-chain fission of steroidal glycosides

The characteristic novel steroidal glycosides of the 23,26-oxygenated spirostanol-type and 16,22-dicarbonyl cholestanol-type obtained in our laboratory underwent the peculiar reactions of side-chain fission between C-22 and C-23 of the steroidal skeleton by acid or alkaline hydrolysis. These reactions would be applied to the structural determination of these sorts of glycosides and suggest the biogenetic pathway of the occurrence of C-22 lactone-type glycosides.