Spergularia marina: a potential source of a novel calcium channel blocker with antihypertensive and diuretic activities.

OBJECTIVE: Spergularia marina (L.) Griseb. (S. marina) is a sub-cosmopolitan species used as traditional phytotherapy based on diverse biological activities. It is native and widespread in the northern hemisphere, though introduced also into the southern hemisphere. The extract of another species 'Spergularia purpurea' has been traditionally used in Morocco against various diseases and S. marina, itself, is a local popular food in South Korea. In this context, we evaluated the potential antihypertensive and diuretic effects of S. marina water and n-butanol extracts in L-NAME-induced hypertensive rats vs. the well-known diuretic, furosemide. MATERIALS AND METHODS: After toxicity studies, selected doses were administered orally daily for one week. Mean arterial blood pressure (MABP), water/electrolyte clearance, renal functions, and serum electrolytes were assessed. Vascular reactivity of isolated aortic rings was evaluated under different incubating settings against various antagonists to unravel the mechanism of action. RESULTS: Both extracts significantly reduced the MABP. Only, the n-butanol fraction exerted a significant aquaresis, increasing electrolyte free-water clearance with a significantly decreased urinary Na+, K+, and C- excretion. The water extract significantly augmented the ACh-induced relaxation and attenuated the NE-induced aortic rings' contractile response. It also exhibited a direct relaxant effect on the NE-precontracted rings with intact or denuded endothelium. Blocking the vascular calcium channels by preincubation with nifedipine prevented the S. marina-induced relaxation, denoting a calcium channel blocking activity. CONCLUSIONS: The vasorelaxant and the differential diuretic effects of both extracts introduce S. marina as a potential novel antihypertensive agent with calcium channel blocking activity. To enrich cardiovascular therapeutics, human studies to confirm the efficacy and safety of S. marina in hypertension are warranted. GRAPHICAL ABSTRACT: https://www.europeanreview.org/wp/wp-content/uploads/Graphical-abstract.jpg.

Physical and geometrical parameters controlling measurements of radon emanation and exhalation from soil.

The influence of physical and geometrical parameters, such as grain size, volume of the emanation container and mass of the sample, on the emanation coefficient and exhalation rates of radon (with and without consideration of back diffusion effect and effective volume of the emanation container) released from soil have been investigated. Moreover, a method for assessing the flux of radon migrate through soil layers was proposed. This method is based on measurement of the cumulative radon concentration transmitted through five layers of soil. The transmission factor results from the decay of 222Rn over a period of 60 day required for it to migrate through these layers was also determined. The soil samples were collected from Al-Marj city located in northeastern Libya. Radon measurements were carried out by using a closed emanation container based on CR-39 nuclear track detectors (NTDs). The results showed that the radon emanation coefficient clearly increases with grain size, container volume and sample mass. The exhalation rates also increase with grain size and sample mass, but the container volume parameter shows an opposite trend. The radon flux and its transmission factor are significantly decreased throughout that uniform soil when the increase in soil depth retarded exhalation. This study shows that various physical and geometrical parameters were demonstrated to be greatly affected on the emanation coefficient and exhalation rates of radon released from soil.

Radon exhalation from Libyan soil samples measured with the SSNTD technique.

Radon concentrations in soil samples collected from the cities of Benghazi and Al-Marj, located in northeastern Libya, were measured using the sealed-can technique based on the CR-39 SSNTDs. Mass and areal radon exhalation rates, radium content and radon concentration contribute to indoor radon, and annual effective doses were determined. The results indicate mostly normal rates, but there were some higher levels of radon concentration and emanation in samples collected from Al-Marj and one sample from Benghazi.

Bioequivalence of two brands of ciprofloxacin 750 mg tablets (Sarf and Ciprobay) in healthy human volunteers.

An open, randomized, two-way crossover study was carried out in 28 healthy volunteers at Gulf Pharmaceutical Industries (Julphar), as a joint venture with Saqr Hospital, Ras Al-Khaimah, UAE. The two commercial brands used were Sarf (Julphar, UAE) as test and Ciprobay (Bayer AG, Germany) as reference product. The drug was administered to each subject with 240 mL of water after an overnight fasting in two treatment days separated by a one-week washout period. After dosing, serial blood samples were collected for a period of 24 hr and serum was separated and analyzed for ciprofloxacin using a sensitive, reproducible, and accurate high-performance liquid chromatography (HPLC) method with ultraviolet (UV) detection. Various pharmacokinetic parameters, including AUC0-t, AUC0-infinity, Cmax, Tmax, t1/2, and lambdaz, were determined from ciprofloxacin serum concentration-time profiles for both formulations and found to be in good agreement with reported values. The parameters AUC0-t, AUC0-infinity, and Cmax were tested for bioequivalence after log-transformation of data. No significant difference was found based on analysis of variance (ANOVA); the 90% confidence intervals (95.73-107.62%, 94.98-108.26%, 92.80-103.90% for AUC0-t, AUC0-infinity, Cmax, respectively) for the test/reference ratios of these parameters were within the bioequivalence acceptance range of 80-125%. Based on this data, it is concluded that both formulations are bioequivalent and are interchangeable in medical practice.

Cycloartane triterpene glycosides from Astragalus trigonus.

Three new cycloartane glycosides, trigonoside I, II and III, and the known astragalosides I and II were isolated from the roots of Astragalus trigonus. The structures of the new glycosides were totally elucidated by high field (600 MHz) NMR analyses as cycloastragenol-6-O-beta-xylopyranoside, cycloastragenol-3-O-[alpha-L-arabinopyranosyl(1-->2)-beta-D- xylopyranosyl]- 6-O-beta-D-xylopyranoside and cycloastragenol-3-O-[alpha-L-arabinopyranosyl (1-->2)-beta-D-(3-O-acetyl)-xylopyranosyl]-6-O-beta-D-xylopyranoside.

Antimicrobial isoflavans from Astragalus species.

Two new antimicrobial isoflavans, 1-[(3R)-7,8-dimethoxybenzopyranyl]-4- hydroxybenzoquinone (astragaluquinone) and (3S)-7,1'-dihydroxy-8,3'-dimethoxyisoflavan (8-methoxyvestitol), and the known 7-hydroxy-2',3',4'-trimethoxyisoflavan were isolated from roots of Astragalus alexandrinus and A. trigonus. The structures of the new isoflavans were established by spectroscopic methods.

Astragalosides from Egyptian Astragalus spinosus Vahl.

Four cycloartane triterpene oligoglycosides were isolated from the n-butanol extract of the aerial parts of Astragalus spinosus Vahl. (Leguminosae). They were identified as astragaloside I (1), isoastragaloside I (2), astragaloside IV (4) and cycloastragenol 6-O-glucoside (5) on the basis of comparing their m.p.'s, 1H NMR and 13C NMR spectra and chromatographic patterns with the data given in the literature. The results of AIDS antiviral and antitumor screening of the major component, astragaloside II (3), are dealt with.

Ascorbate in the treatment of experimental transplanted melanoma.

Sodium ascorbate supplementation in drinking water inhibited subcutaneous tumor growth, enhanced levodopa methylester (LDME) chemotherapy, and increased survival of B16 melanoma-bearing mice. Antitumor activity was greatest in mice fed diets low in tyrosine and phenylalanine (restricted diet). Ascorbate partially protected against LDME-induced decrease in food intake. Primary tumor masses were smaller, more well defined, and less invasive in ascorbate-supplemented mice, and secondary tumor masses appeared encapsulated. Dehydroascorbate increased tumor growth and decreased survival. Ascorbate supplementation did not alter establishment of experimental B16-BL6 melanoma metastases but inhibited tumor outgrowth when combined with LDME chemotherapy and the restricted diet. Spontaneous metastasis was inhibited by ascorbate in mice fed the restricted diet. Ascorbate supplementation doubled plasma concentration in melanoma-bearing mice independent of diet and increased tumor concentration 3.7-fold (basal diet) and 5.6-fold (restricted diet) relative to unsupplemented mice. Tumor peroxidation also increased during ascorbate supplementation and LDME treatment.

Specificity of the suppression of metastatic phenotype by tyrosine and phenylalanine restriction.

Amino acid restriction modulates tumor growth, although effects on metastasis are poorly documented. We demonstrate that low levels of tyrosine (Tyr) and phenylalanine (Phe) suppress metastasis of B16-BL6 melanoma and that these effects are specific to these two amino acids. Weight loss and sustained low body weight in mice fed low Tyr and Phe diet do not contribute to the antimetastatic effects. Furthermore, methionine (Met) restriction, which decreased survival of mice inoculated i.p. with B16 melanoma, only slightly inhibited spontaneous metastasis compared to the dramatic inhibition during Tyr and Phe restriction. Tyr and Phe restriction inhibited spontaneous metastasis by impairing the ability of tumor cells to establish metastatic foci and not via differential tumor cell removal from the blood. Spontaneous metastasis is blocked by Tyr and Phe intervention even in mice with established lymph node tumors. Tumors isolated from mice fed low Tyr and Phe diet reinoculated into mice fed normal diet exhibited lower experimental metastatic potential, reflected by decreased formation of lung tumor colonies and increased survival of inoculated mice. This decrease in metastatic potential is not associated with tumor chemosensitivity. These findings indicate that Tyr and Phe restriction could become an important adjuvant to effective melanoma treatment.

Toxicity of chronic high alcohol intake on mouse natural killer cell activity.

The toxicity of chronic alcohol intake on natural killer (NK) cell activity of spleen cells from well-nourished, female C57BL/6 mice was studied in a 4-hour cytolytic chromium-release assay against YAC-1 lymphoma cells. Mice were fed a nutritionally complete crystalline amino acid diet and received 20% w/v alcohol solution for 12 weeks. Ad libitum and pair-fed control mice were given diet and either an isocaloric glucose solution or water. Decreased NK cell activity was observed in alcohol-consuming mice relative to all other control groups. NK cell activity was moderately decreased by feeding mice a high glucose diet, but more severely lowered in pair-fed groups compared to ad libitum control groups.

Response of natural killer cells from dietary tyrosine- and phenylalanine-restricted mice to biological response modifiers.

The effect of dietary tyrosine and phenylalanine restriction on splenic natural killer (NK) cell activity was studied in tumor-free B6D2F1 and NIH nude mice and in B16 bladder-6 (BL6) melanoma-bearing B6D2F1 mice. This dietary restriction was found to suppress the naturally elevated NK-cell activity of nude mice and to induce a specific lymphocytopenia in B6D2F1 mice fed the restricted diet for a prolonged period. Baseline NK-cell activity was significantly lower in tumor-free B6D2F1 mice fed a diet restricted in tyrosine and phenylalanine (restricted diet) than in tumor-free mice fed a basal diet. Similar kinetics of activation after a single i.p. injection of 100 micrograms of polyinosinic:polycytidylic acid (poly I:C) were observed in mice fed both diets. NK-cell activity was not significantly augmented after i.v. inoculation of BL6 melanoma, irrespective of the diet fed; however, it was enhanced in tumor-bearing mice after poly I:C injection. This augmentation was similar to that observed in tumor-free mice. Spleen cells from mice fed either diet were responsive to stimulation of NK-cell activity after in vitro incubation with interleukin-2. These results indicate that dietary restriction of tyrosine and phenylalanine, a potentially useful therapeutic adjunct known to lower NK-cell activity, does not significantly interfere with poly I:C or interleukin-2 induction of NK cells. Our results also demonstrate that, while this dietary restriction causes lymphocytopenia, no effect of the diet could be found on total serum IgG or circulating immune complex levels.

Dietary restriction of tyrosine and phenylalanine: inhibition of metastasis of three rodent tumors.

The effects of a combined dietary restriction of tyrosine and phenylalanine on metastasis were investigated with the use of 3 rodent tumor cell lines: B16-bladder 6 (BL6) melanoma inoculated into (C57BL/6 X DBA/2)F1 mice, Lewis lung (3LL) carcinoma inoculated into C57BL/6 mice, and RT7-4bs hepatocarcinoma inoculated into BD-IV rats. When examined for effects on spontaneous metastasis, dietary restriction of tyrosine and phenylalanine had no effect on metastasis to draining lymph nodes in either BL6 or 3LL tumors. However, the restriction did reduce metastasis of RT7-4bs cells to draining lymph nodes by 60%. In all tumor systems, the dietary restriction effectively inhibited the subsequent growth of lymph node tumors. The most marked effect of the dietary restriction was on spontaneous hematogenous metastasis, which was almost totally blocked for BL6 cells and was reduced by 85% for RT7-4bs cells. Tumor-associated splenomegaly also was completely inhibited in 3LL tumor-bearing mice. The selective dietary amino acid restriction failed to reduce initial lung colonization in the experimental metastasis assay but clearly inhibited subsequent tumor outgrowth in the lungs. These findings demonstrate that modification of host nutritional status by restriction of the dietary intake of tyrosine and phenylalanine exerts a dramatic antimetastatic effect directed particularly on spontaneous hematogenous metastasis. Although the preliminary data suggest a primary modulating effect on tumor cell populations growing in diet-restricted animals to reduce inherent metastatic ability, the actual mechanisms remain to be defined.

Interaction between specific dietary factors and experimental chemotherapy of metastatic melanoma.

The single and combined effects of (a) dietary restriction of phenylalanine and tyrosine, (b) levodopa methylester chemotherapy, and (c) megadose sodium ascorbate supplementation on experimental metastasis was determined in B16-BL6 melanoma. Dietary restriction and levodopa methylester therapy inhibited tumor outgrowth, whereas ascorbate alone was inactive. In combination, however, the effect of dietary restriction and levodopa methylester chemotherapy was augmented by sodium ascorbate. Tumor cells surviving this combination therapy (treated population) were isolated from the lungs of treated mice, and proved to be tumorigenic when inoculated SC into the back of naive mice. The resulting tumors grew more slowly than those produced by inoculation of similarly isolated control cells (control population), irrespective of whether the diet was adequate or deficient in phenylalanine and tyrosine. Failure of the treated tumor cell population to exhibit reduced sensitivity to the combination chemotherapy or, unlike the control population, to exhibit variation in pigmentation levels, suggests that the restriction of phenylalanine and tyrosine during drug therapy alters the tumor response to reduce heterogeneity and perhaps interferes with the emergence of drug resistance.

Alcohol and related dietary effects on mouse natural killer-cell activity.

Natural killer (NK) cell activity of spleen cells from female C57BL/6 mice receiving 10% w/v alcohol solution for 4 weeks was studied in mice fed a nutritionally complete crystalline amino-acid diet and in mice fed diets moderately deficient in (i) tyrosine and phenylalanine or (ii) methionine. Natural killer cell activity was determined in a 4-hr cytolytic chromium-release assay against YAC-1 lymphoma cells. Alcohol consumption did not effect NK cell-mediated lysis irrespective of nutritional status; however, NK-cell activity was depressed in mice fed the tyrosine- and phenylalanine-deficient diet and was enhanced in mice fed the methionine-deficient diet. These data suggest that the changes in immune function often observed in alcoholics may be more closely linked to dietary and nutritional status than to the direct effects of the ingested alcohol.