Band 26, Heft 5

Na + /H + exchangers (NHEs) are the transporter proteins that play an important role in intracellular pH (pH i ) regulation, cell differentiation and cell volume and that mediate transepithelial Na + and HCO 3 − absorption on the basis of chemical gradients across the plasma membrane. Its activation causes an increase in intracellular Na + , which further leads to Ca + overload and cell death. The pharmacological inhibition of these transporter proteins prevents myocardial infarction and other heart diseases like congestive heart failure in experimental animal models as well as in clinical situations. The more recent studies have implicated the role of these exchangers in the pathophysiology of brain diseases. Out of nine NHE isoforms, NHE-1 is the major isoform present in the brain and regulates the trans-cellular ion transport through blood-brain barrier membrane, and alteration in their function leads to severe brain abnormalities. NHEs were shown to be involved in pathophysiologies of many brain diseases like epilepsy, Alzheimer’s disease, neuropathic pain and ischemia/reperfusion-induced cerebral injury. Na + /H + -exchanger inhibitors (e.g., amiloride and cariporide) produce protective effects on ischemia/reperfusion-induced brain injury (e.g., stroke), exhibit good antiepileptic potential and attenuate neuropathic pain in various animal models. The present review focuses on the pathophysiological role of these ion exchangers in different brain diseases with possible mechanisms.

Recent concerns on increased incidence of myocardial infarction and stroke on administration of calcium and vitamin D supplements have alarmed the physicians about safety of these drugs. Although both calcium and vitamin D have been shown in the past to have beneficial effect on cardiovascular disease status through lowering of harmful lipids, these findings have been contradicted by some recent meta-analysis and randomized controlled trials that have shown no beneficial or in some cases a deteriorating effect of these supplements on lipid levels. In particular, calcium supplementation has been associated more with increased incidence of cardiovascular morbidity than vitamin D, but the convincing proof is still lacking. Here we have highlighted the results of some significant studies that might impact the prescription of these drugs.

Background: Human health is affected by space weather component [solar (SA), geomagnetic (GMA), cosmic ray (CRA) – neutrons, space proton flux] activity levels. The aim of this study was to check possible links between timing of human (both genders) monthly deaths distribution and space weather activity. Methods: Human deaths distribution in the Republic of Lithuania from 1989 to 2013 (25 years, i.e., 300 consecutive months) was studied, which included 1,050,503 deaths (549,764 male, 500,739 female). Pearson correlation coefficients ( r ) and their probabilities (p) were obtained for years: months 1–12, sunspot number, smoothed sunspot number, solar flux (2800 MGH, 10.7 cm), adjusted solar flux for SA; A, C indices of GMA; neutron activity at the earth’s surface (imp/min) for CRA. The cosmophysical data were obtained from space science institutions in the USA, Russia and Finland. The mentioned physical parameters were compared with the total number of deaths, deaths from ischemic heart disease (n=376,074), stroke (n=132,020), non-cardiovascular causes (n=542,409), accidents (n=98,805), traffic accidents (n=21,261), oncology (n=193,017), diabetes mellitus (n=6631) and suicide (n=33,072). Results: Space factors were interrelated as follows for the considered period: CRA was inversely related to SA and GMA, CRA/SA ( r =−0.86, p>0.0001), CRA/GMA ( r =−0.70, p<0.0001); SA and GMA were correlated ( r =0.50, p<0.0001). The total deaths distribution was inversely related to SA ( r =−0.31, p<0.0001) and correlated with CRA (neutron) activity ( r =0.234, p<0.0001). Ischemic heart disease (IHD) deaths (most at home) show a drop yearly ( r =−0.2551), more for men. It was correlated with GMA for the total IHD population and men. Stroke deaths were inversely related to SA ( r =−0.38, p<0.0001) and correlated with CRA ( r =0.41, p<0.0001) and year ( r =0.49, p<0.0001), showing a steady rise. The IHD/stroke deaths ratio was negatively correlated with the years of observation ( r =−0.754, p=0.0001). Non-cardiovascular deaths were inversely related to SA ( r =−039, p<0.0001) and correlated with CRA ( r =0.263, p<0.0001). Oncology deaths that now are dominating in many places were inversely related to SA ( r =−0.475, p<0.0001) and correlated with CRA ( r =0.426, p<0.0001). Suicide showed a drop with years ( r =−0.29, p<0.0001), possibly related to excessive immigration of young population (18–34 years) in the last decade and correlated with two of three GMA indices. Traffic accidents were correlated with SA and GMA ( r =0.392–0.461, p<0.0001) and inversely related to CRA ( r =−0.436). Conclusions: Most groups of deaths are related to space weather component activity. Extreme levels of activities of both groups (SA, GMA, and opposite CRA – neutron) are related to some health risks. In the considered period, there were relatively few GMA storms and low GMA was dominating, accompanied by higher CRA (neutron) activity. The ways of action of the components of space weather on the human body need additional studies. There is a special need for the prevention of rising cerebral vascular accidents and oncology malignancies as the causes of death.

Background: Bronchial asthma and chronic obstructive pulmonary disease (COPD) are the major obstructive disorders that may contribute to the severity in individual patients. The present study was designed to compare the efficacy and safety of theophylline and doxofylline in patients with bronchial asthma and COPD. Methods: A total of 60 patients, 30 each with bronchial asthma and COPD, were enrolled for the study. Each group of 30 patients received standard treatment for asthma and COPD. Each group was again subdivided into two with 15 patients each, who received theophylline or doxofylline in addition to standard therapy, for a period of 2 months. Each patient was followed up fortnightly for the assessment of efficacy parameters using a pulmonary function test (PFT), clinical symptoms and emergency drug use, and safety was assessed by recording adverse drug reactions. Results: Both theophylline and doxofylline produced enhancements in PFT at different time intervals in both asthma and COPD patients. The maximum beneficial effects were seen at 6 weeks for asthma patients and at 8 weeks for COPD patients for both theophylline and doxofylline. Conclusions: The comparative study showed that doxofylline was more effective as evidenced by improvement in PFT as well as clinical symptoms, and reduced incidence of adverse effects and emergency bronchodilator use.

Background: Plant-derived phytochemicals consisting of phenols and flavonoids possess antioxidant properties, eventually rendering a lucrative tool to scavenge reactive oxygen species. This study was carried out to evaluate in vitro antioxidant and cytotoxic potential of methanolic extract and petroleum ether extracts of Smilax zeylanica L. stems. Methods: Phytochemical screening was done following standard procedures. Antioxidant activity was tested using several in vitro assays, viz., 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, NO assay, H 2 O 2 assay, CUPRAC assay, FRAP assay and total antioxidant capacity assay. Total phenol and flavonoid contents were determined by colorimetric method. Brine shrimp lethality and MTT cell viability assays were used for cytotoxic potential. Results: Preliminary phytochemical study revealed the presence of flavonoids and glycosides in both extracts. Methanolic extract was found to possess stronger antioxidant potential than petroleum ether extracts in all assays. The IC 50 value of methanolic extract was 29.14±0.39 μg/mL, 120.30±3.32 μg/mL and 78.41±5.53 μg/mL in DPPH assay, NO assay and H 2 O 2 assay, respectively. Likewise, total phenol [56.78 mg/g gallic acid (GAE)] and flovonoid [125.69 mg/g quercetin equivalents (QE)] were higher in methanolic extract. In cytotoxicity assays, petroleum ether extract showed stronger activity in both brine shrimp lethality (LC 50 2.85±0.13 μg/mL) and MTT cell viability assay (IC 50 15.49±1.18 μg/mL). Conclusions: These findings demonstrate that methanolic extracts could be considered as potential sources of natural antioxidant, whereas petroleum ether extracts could be explored for promising anticancer molecules.

Background: Daniella oliveri is a deciduous plant that is commonly found in savanna and open grassland. Various parts of the plant is used by herbalist in the management of different ailments. The present study aims at investigating the hepatoprotective and antioxidant activity of the methanolic extract of D. oliveri leaves. Methods: The hepatoprotective activity was investigated using carbon tetrachloride (CCl 4 )-induced hepatotoxicity in albino rats. The antioxidant activity was determined using both in vitro (2, 2-diphenyl-1-picrylhydrazine photometric assay) and in vivo (malondialdehyde and catalase level assay) models. Results: The pretreatment with extract (100, 200, and 400 mg/kg) and silymarin (100 mg/kg) produced a significant (p<0.05) dose-dependent increase in hepatoprotective activity when compared with the negative control group. The extract (25–400 μg/mL concentration) produced a concentration-dependent increase in antioxidant activity in 2, 2-diphenyl-1-picrylhydrazine (DPPH) photometric assay. The IC 50 of the extract in DPPH photometric assay was 400 μg/mL concentrations. The extract and silymarin showed a significant (p<0.05) dose-dependent increase in catalase level in treated rats when compared with the negative control group. Also, the extract and silymarin produced a significant (p<0.05) dose-dependent decrease in malondialdehyde level in treated rats when compared with the negative control group. Conclusions: The results of the study suggest that D. oliveri leaves has a potent hepatoprotective activity that may be linked to its antioxidant activities and validates its use in the traditional management of liver disorders.

Background: Citrus peels are consumed in the form of infusions, candy or wine, based on their well-documented nutritional and medicinal properties. This study sought to investigate the effect of some citrus peels’ [grapefruit ( Citrus paradisii ), orange ( Citrus sinensis ) and shaddock ( Citrus maxima )] extracts on matrix metalloproteinase (MMP) and proteasome activities in primary human colonic tumor (Caco-2) and the metastatic cell lines (LoVo and LoVo/ADR) in a bid to explain the possible mechanism by which the peels could manage/prevent colon cancer. Methods: The inhibition of MMP and proteasome activities in the cells by the peel extracts, as well as the identification of phenolic compounds using high-performance liquid chromatography with diode-array detection (HPLC-DAD), was determined. Results: Orange peel extracts had the strongest inhibition of MMP in Caco-2 and LoVo cells, while shaddock had the least. Shaddock peel extracts also had the least MMP inhibition in LoVo/ADR lysates. Grapefruit had the least proteasome inhibition in Caco-2 and LoVo lysates, while there was no significant (p>0.05) difference in the proteasome inhibition of the peel extracts in LoVo/ADR lysates. The extracts inhibited proteasome activity in extract-treated cells, and HPLC fingerprinting of the extracts revealed the presence of some phenolic compounds such as quercetin, caffeic acid, kaempferol, catechin and naringin. Conclusions: The inhibition of MMP and proteasome activities in colon cancer cell lines suggests the potential use of citrus peels as functional food in the management and/or prevention of colon cancer.

Background: The objective of this work was to study the analgesic and anti-inflammatory activity of Tectona grandis Linn. (TG) stem extract. Methods: Healthy albino rats (150–200 g) and mice (25–50 g) were arranged and divided into five groups. Group 1 received distilled water and served as control, groups 2, 3, 4 were treated with TG stem extract (100, 200, 400 mg/kg) and group 5 received standard drug. For analgesic activity, the radiant heat method and writhing test were used, and for anti-inflammatory activity, the paw oedema model and granuloma pouch method were used. Statistical analysis was done by one-way analysis of variance followed by the t-test. Results: In the radiant heat method, there was a dose-dependent increase in reaction time in TG stem extract (100, 200, 400 mg/kg) and standard drug (buprenorphine). In the writhing test, TG stem extract (200, 400 mg/kg) and aspirin decreased the number of writhes which was significant (p<0.01, p<0.001) as compared to controls. The percentage protection was 8.88%, 15.55%, 22.22% and 35.55% in groups 2, 3, 4 and 5, respectively. In the rat paw oedema test, TG stem extract (200, 400 mg/kg) and aspirin showed 20%, 40% and 54% inhibition of oedema which was statistically significant (p<0.05, p<0.01, p<0.001), respectively, as compared to control at the end of 4 h. In the granuloma pouch method, TG stem extract (100, 200, 400 mg/kg) and aspirin showed 13.33%, 22.22%, 33.33% and 66.66% inhibition of granuloma, respectively, which was significant (p<0.05, p<0.01, p<0.001). Conclusions: TG stem extract possesses significant anti-inflammatory and analgesic activity.

Background: Since centuries, Cyperus rotundus L. has been used against gastric ailments in traditional Indian medicine, especially in Ayurveda and Siddha. Therefore, it is very obvious that this plant will have a greater potential to treat gastric ulcers. For this reason, in this study, we mainly focused on the ulcer-preventive role of C. rotundus in rats treated with non-steroidal anti-inflammatory drugs. Methods: Seventy percent methanolic extract of the plant was prepared and fed to 36-h fasted rats. Ulcer was induced in these rats by single oral administration of aspirin (400 mg/kg) 1 h after the administration of the plant extract. After 4 h, the rats were sacrificed, ulcer index was calculated, and antioxidant activity of the extract in gastric mucosa was evaluated by determining the levels of superoxide dismutase, glutathione, glutathione peroxidase, and tissue lipid peroxidation. Results: Oral administration of different doses of C. rotundus rhizome methanolic extract (CME; 250 mg/kg and 500 mg/kg) significantly inhibited aspirin-induced gastric ulceration in animals in a dose-dependent manner (49.32% and 53.15%, respectively), which was also comparable with the standard gastric ulcer drug ranitidine. Administration of CME also significantly increased the activity of superoxide dismutase, cellular glutathione and glutathione peroxidase, and inhibited the lipid peroxidation in the gastric mucosa of ulcerated animals in a dose-dependent manner. Conclusions: Our results showed that C. rotundus extract has the capacity to significantly inhibit aspirin-induced gastric ulcers through an antioxidant defense mechanism. This study warrants further examination of this plant for its gastroprotective activities.

Background: Moringa oleifera Lam (Moringaceae) is a highly valued plant, distributed in many countries of the tropics and subtropics. It has an impressive range of medicinal uses with high nutritional value. Methods: The commercially processed M. oleifera was extracted using methanol as its solvent. Phytochemical analysis as well as the anti-oxidant properties of this supplement were also investigated. Acute toxicity was carried out in fasted mice. Carrageenan and histamine tests were used to assess anti-inflammatory effects in rats, while analgesic activities were assessed using the acetic acid-induced writhing test and formalin-induced paw lick test in mice. In the anti-oxidant tests, 1,1-diphenyl-2-picrylhydrazyl, ferrous reducing activity power, 2,2 1 -azinobis-(3-ethylbenthialozine)-6-sulphonic acid and total polyphenolic (TPP) assays were deployed at concentrations of 10 mg/mL and 20 mg/mL. Results: The phytochemical analysis showed that the extract contained flavonoids, terpenoids, glycosides, tannins and saponins. In the acetic acid-induced writhing test, the extract significantly reduced the number of writhes at 100 and 200 mg/kg but not so much at 50 mg/kg. In the formalin-induced paw lick test, the effect was similar to that of the acetic writhing test. The analgesic effects were comparable to that of indomethacin used at 10 mg/kg. In the anti-inflammatory test, the extract reduced the formation of oedema especially at a dose of 200 mg/kg. In the anti-oxidant test, the extract was found to possess a free radical-scavenging property and is concentration related. Conclusions: The use of this extract for medicinal and nutritional purposes may have thus been justified; however, caution must be exercised in its use to prevent the toxic effect.

Background: Jobelyn ® (JB) is an African sorghum-based food supplement claimed to be efficacious for the treatment of rheumatoid arthritis (RA). Although in vitro studies confirmed its anti-inflammatory property, no study had shown the effect of JB using in vivo animal models of inflammation. Thus, its effects on acute and chronic inflammation in rats were evaluated in this study. Its effect on rat red blood cell (RBC) lysis was also assessed. Methods: Acute inflammation was induced with intraplanter injection of carrageenan and increase in rat paw volume was measured using plethysmometer. The volume of fluid exudates, number of leukocytes, concentrations of malondialdehyde (MDA), and glutathione (GSH) in the fluid were measured on day 5 after induction of chronic inflammation with carrageenan in the granuloma air pouch model. RBC lysis induced by hypotonic medium as determined by release of hemoglobin was measured spectrophotometerically. Results: JB (50–200 mg/kg) given orally produced a significant inhibition of acute inflammation induced by carrageenan in rats. It reduced the volume and number of leukocytes in inflammatory fluid in the granuloma air pouch model of chronic inflammation. It further decreased the levels of MDA in the fluid suggesting antioxidant property. JB elevated the concentrations of GSH in inflammatory exudates indicating free radical scavenging activity. It also significantly inhibited RBC lysis caused by hypotonic medium, suggesting membrane-stabilizing property. Conclusions: JB has in vivo anti-inflammatory activity, which may be related to its antioxidant and membrane-stabilizing properties, supporting its use for the treatment of arthritic disorder.

Background: Estrogen-mediated uterus endometrium instability is considered as one of the etiological factors in dysfunctional uterine bleeding (DUB) and uterine cancer. Saraca asoca (Family: Fabaceae) and its fermented preparation, Asokarishta , are extensively used as uterine tonic to treat gynecological disorders in Ayurveda. The present study evaluated the effect of S. asoca (Asoka) on estrogen-induced endometrial thickening of rat uterus. Methods: Endometrial thickening was induced by intraperitoneal injection of estradiol (20 μg/kg b.wt) to 8-day-old immature rats for alternate 5 days. Methanolic extract (200 mg/kg b. wt) from S. asoca bark was given orally along with estradiol. Uterus endometrial thickening was analyzed histopathologically and serum estrogen level by radioimmunoassay (RIA). Cyclooxygenase (COX-2) expression in rat uterus was also estimated by Western blot. Anti-inflammatory activity of the extract was analyzed by formalin- and carrageenan-elicited paw edema models in mouse. Results: Uterus endometrium proliferation and keratinized metaplasia with seven to eight stratified epithelial layers on day 16 was observed in rats administered with estradiol. Treatment with S. asoca reduced the thickening to two to four layers and the serum estrogen level diminished significantly to 82.9±12.87 pg/mL compared to rats administered with estrogen alone (111.2±10.68 pg/mL). A reduction of formalin- and carrageenan-induced paw edema in mouse by S. asoca extract was observed. Lower level of lipopolysaccharides (LPS)-induced COX-2 enzyme in rat uterus by the extract further confirms its anti-inflammatory activity. Conclusions: Present study reveals the antiproliferative and antikeratinizing effects of S. asoca in uterus endometrium possibly through its anti-estrogenic and anti-inflammatory properties.

Background: Different compounds of smoking (e.g., nicotine and cotinine) are risk factors for various diseases such as oral cancer and periodontal diseases. Some studies reported the negative effects of nicotine on cell proliferation and differentiation. The present in vitro study assessed the effects of nicotine and cotinine (long-acting metabolite of nicotine) on the attachment and viability of human gingival fibroblast (HGF) cells to tooth root surfaces. Methods: A total of 70 teeth specimens were placed into 48-well culture plates and covered with HGF cell suspension, in complete Dulbecco’s modified Eagle’s medium culture medium containing 1 nM, 1 μm, 1 mM, and 5 mM of nicotine and cotinine concentrations. Cellular attachment and viability measured using an MTT assay and a scanning electron microscope were used for cell morphological evaluation. Results: After 24 h, low (nanomolar and micromolar) and high concentrations (millimolar) of nicotine and cotinine caused a significant reduction in the initial cell adhesion in comparison with the control group, but no significant difference was observed between the nicotine and the cotinine groups (p<0.05). Dentally attached cells with low concentrations of nicotine and cotinine proliferated 48 h after exposure, the same as the control group. However, dentally attached cells with high concentrations of nicotine and cotinine (especially 5 mM) did not proliferate 24 h after exposure (p<0.05). Conclusions: Low concentrations of nicotine and cotinine caused a reduction in the initial cell adhesion. However, no significant adverse effects on the proliferation of attached cells were seen in the longer period. High concentrations of nicotine and cotinine have adverse effects on the cell adhesion and proliferation of HGF cells.