Clinical profile of functional constipation in Saudi children.

BACKGROUND: Functional constipation (FC) is a common condition in children, and information on the clinical characteristics of FC in Saudi children is scarce. OBJECTIVE: Describe the clinical profile of FC in Saudi children. DESIGN: Retrospective. SETTING: Hospital that provides primary, intermediate and tertiary care. PATIENTS AND METHODS: All children diagnosed with FC according to the Rome IV criteria were included and had at least one follow-up clinic visit. Demographic and clinical data collected from medical records included the age at onset, duration of constipation, clinical features, treatment modalities, and factors associated with clinical response. Descriptive statistics and Pearson's chi-squared test were used in the statistical analysis to see how categorical study variables were linked to clinical response. A P value of ≤.05 was used to report statistical significance. MAIN OUTCOME MEASURE: Compliance and clinical response to polyethylene glycol (PEG) compared with lactulose. SAMPLE SIZE: 370 children from 0.1 to 13 years of age. RESULTS: The median (IQR) age of onset was 4 (5) years and less than one year in 14%. The median (IQR) duration of constipation was 4 months (11) and less than two months in 93/370 (25%). Abdominal pain was the most commonly associated feature (44%). Screening for celiac disease and hypothyroidism was negative. A Fleet enema was the most common disimpaction method (54%) and PEG was the most common maintenance medication (63.4%). PEG was significantly better tolerated (P=.0008) and more effective than lactulose (P<.0001). Compliance was the only variable significantly associated with clinical response. CONCLUSIONS: PEG was better tolerated and more effective than lactulose in our study, a finding in agreement with the literature. Therefore, PEG should be the drug of choice in the initial management of FC in Saudi children. Prospective studies on the causes of noncompliance are needed to improve the response to treatment. LIMITATIONS: The limitations of retrospective design are missing data, recall bias, and hospital-based limitation, such as missing milder cases treated at the outpatient level. However, the sample size of 370 may have minimized these limitations.

Ipomoea hederacea Jacq.: A plant with promising antihypertensive and cardio-protective effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Seeds of Ipomoea hederacea Jacq. (family: Convolvulaceae) are traditionally used to treat high blood pressure and cardiac diseases. AIM OF THE STUDY: Present study was conducted to validate the traditional claim and explore the possible mechanism(s) of antihypertensive effects of I. hederacea. MATERIALS AND METHODS: Aqueous-ethanolic extract and activity based fractions of I. hederacea were evaluated using invasive blood pressure measuring technique, isolated tissue experiments, fructose induced hypertension/metabolic syndrome and biochemical analysis.Phytochemical analysis of active fraction was performed with aim to identify chemical composition of I. hederacea seeds. LC-MS analysis was also performed to identify the compounds proposed to be present in active fraction of I. hederacea seeds. RESULTS: Crude extract/fractions of I. hederacea showed dose (0.01-100 mg/kg) dependent significant hypotensive effect in normotensive anesthetized rats, similar to verapamil (0.01-30 mg/kg). Pretreatment with hexamethonium and atropine mediated no significant changes in hypotensive effect of butanol fraction of I. hederacea (Ih.Bn) at 3 mg/kg dose. However, a significant decrease in the hypotensive effect of Ih.Bn 3 mg/kg (-34.82 ± 3.36%; p < 0.05) was observed in the presence of L-NAME (20 mg/kg). Similarly, Ih.Bn (3 mg/kg) showed no significant effect on angiotensin-II response. However, response of phenylephrine (45.60 ± 9.63%; p < 0.05) and dobutamine (18.25 ± 2.10%; p < 0.01) was significantly decreased in the presence of Ih.Bn 3 mg/kg. Ih.Bn also exhibited dose dependent (0.01-100 mg/kg) antihypertensive effect in fructose induced hypertensive rats, similar to verapamil (0.01-30 mg/kg). Concomitant treatment with Ih.Bn (3, 10 and 30 mg/kg) for six weeks showed a dose dependent profound protection with significant (p < 0.01) effect at 30 mg/kg against fructose induced basal mean arterial pressure (142.2 ± 4.62 mmHg). Ih.Bn did not significantly change response of PE, Ang-II and Epi was observed in invasive and ex vivo techniques. However, Ih.Bn significantly (p < 0.01; p < 0.001) prevented against decrease in vascular response of acetylcholine in anesthetized rats and in isolated aorta of rat. A significant dose dependent decrease in triglyceride and glucose level (p < 0.001), and increase in HDL level (p < 0.05) was observed in Ih.Bn treated groups. Results of LC-MS analysis of Ih.Bn showed the presence of 24 compounds that belong to different chemical classes, including carboxylic acid, flavonoids, oligopeptides and tripeptide that are known to have antihypertensive and vasorelaxant properties. CONCLUSIONS: Results of present study indicate the presence of hypotensive/antihypertensive effect in crude extract/fractions of I. hederacea with most potent effect shown by butanol fraction (Ih.Bn), possibly mediated through α1 blocking, ß blocking and iNOS/cGMP stimulating activity.

Role of the NO/cGMP pathway and renin-angiotensin system in the hypotensive and diuretic effects of aqueous soluble fraction from Crataegus songarica K. Koch.

ETHNO-PHARMACOLOGICAL RELEVANCE: Fruits of Crataegus songarica K. Koch. (Rosaceae) are commonly used in folk medicine for their diuretic properties to treat hypertension and congestive heart failure. To date, no scientific data has been published to support the diuretic potential. AIM OF THE STUDY: The purpose of this study was to evaluate efficacy and mechanism underlying the hypotensive and diuretic action of C. songarica in normotensive rats and to determine the constituents from the extracts by LC-DAD-MS. MATERIALS AND METHODS: Firstly, phytochemical profiling and antioxidant potential of C. songarica extracts was determined. Then, to evaluate changes in blood pressure, different groups of anesthetized normotensive rats were intravenously treated with crude extract (CS-Cr, 10-80 mg/kg), aqueous soluble (AS-CS, 0.1-20 mg/kg), and n-butanol soluble fractions of C. songarica (BS-CS, 1-80 mg/kg). The diuretic effects of CS-Cr (100-500 mg/kg, p.o), AS-CS (100-300 mg/kg, p.o) and BS-CS (100-300 mg/kg, p.o) were evaluated in comparison with hydrochlorothiazide (HCTZ, 10 mg/kg, p.o). The urinary volume, sodium, potassium and pH were estimated in the sample collected for 6 h from saline-loaded rats. Using pharmacological antagonists or inhibitors, we determine the involvement of acetylcholine, prostaglandins, and nitric oxide in C. songarica induced hypotensive and diuresis action. In addition, the activities of angiotensin converting enzyme, erythrocytary carbonic anhydrase and renal Na+/K+/ATPase were evaluated in vitro. RESULTS: From the LC-DAD-MS analyses, thirty-nine compounds were detected, showing a complex chemical profile and an expressive antioxidant activity "in vitro". Acute treatment with CS-Cr, AS-CS, and BS-CS exhibited significant hypotensive and diuretic potential in normotensive rats. However, AS-CS produced most potent and significant dose-dependent hypotension in normotensive rats, and also produced highly significant diuretic and saluretic effects. Despite the changes in urinary excretion of electrolytes, the plasmatic levels of sodium and potassium were not changed. Previous treatment with atropine and L-NAME significantly reduced the hypotensive and diuretic action of AS-CS in normotensive rats. Moreover, the 7-day treatment with AS-CS also resulted in significant ACE inhibitory activity. CONCLUSION: This research supports and extends the ethnomedicinal use of C. songarica as diuretic and hypotensive agent. The results showed that AS-CS from C. songarica could present compounds responsible for hypotensive and diuretic activities with no signs of toxicity, and these effects could involve nitric oxide pathway activated by muscarinic receptors or/and inhibition of angiotensin converting enzyme.

Ribes orientale: A novel therapeutic approach targeting rheumatoid arthritis with reference to pro-inflammatory cytokines, inflammatory enzymes and anti-inflammatory cytokines.

ETHNOPHARMACOLOGICAL RELEVANCE: The roots of Ribes orientale (Family Grossulariaceae) have long been used as a folk remedy to treat rheumatism and joints pain in Northern Areas of Pakistan. AIM OF THE STUDY: The purpose of study was to observe the preventive efficacy of roots of Ribes orientale (RO) aqueous ethanolic extract (30:70) and its aqueous and n-butanol fractions in treating rheumatoid arthritis and to determine its possible mechanism of action. MATERIAL AND METHODS: Arthritis was evaluated in vitro using heat induced bovine serum albumin and egg albumin denaturation and membrane stabilizing assays at 50-6400 µg/ml concentration of extract/fractions whereas, in vivo arthritis was evaluated at 50, 100, 200 mg/kg doses of extract/fractions in formaldehyde model by measuring rat paw volume/diameter. Moreover, highest effective dose (200 mg/kg) of extract/fractions was evaluated in Freünd complete adjuvant (FCA) model. Arthritis was induced in Sprague Dawley rats by immunization with 0.1 ml FCA in left footpad. RO extract/fractions at 200 mg/kg were orally administered from day 0, 30 min prior to adjuvant injection and sustained for 28 days. Paw volume/diameter, arthritic score, body weight, and hematological (WBC, RBC, ESR, Hb and Platelet count) and biochemical (AST, ALT, ALP, urea, creatinine, CRP and RF) parameters were observed. The mRNA expression levels of COX-2, IL-1ß, IL-6, NF-kB, TNF-α, IL-4 and IL-10 were measured by real time reverse transcription polymerase chain reaction (RT-PCR) whereas, PGE2 and TNF-α levels in serum samples were measured by Enzyme linked immunosorbent assay (ELISA). Furthermore, radiographs of hind paws and histological changes in ankle joint were analyzed in adjuvant injected rats. The anti-oxidant activity of plant extract and fractions was evaluated using DPPH and reducing power assays. In addition, phytochemistry, total phenolic and flavonoid contents, and HPLC analysis of most active fraction (aqueous fraction) were performed. RESULTS: Results showed that RO extract and fractions (notably aqueous fraction) significantly reduced protein denaturation and protected erythrocyte membrane in concentration dependent manner. Similarly, extract/fractions induced dose-dependent decrease in paw volume/diameter in the formaldehyde model. Plant extract and fractions significantly suppressed paw swelling and arthritic score, prevented cachexia and remarkably ameliorated hematological and biochemical changes. Furthermore, RO extract/fractions downregulated gene expression levels of PGE2, COX-2, IL-1ß, IL-6, NF-kB and TNF-α whereas, upregulated those of IL-4 and IL-10, compared with FCA control rats. The radiographic and histopathologic improvement in joint architecture was also observed in RO treated rats. Piroxicam, used as reference drug, also significantly suppressed arthritis. Additionally, plant exhibited notable anti-oxidant activity and phytochemical analysis revealed the presence of flavonoids and polyphenols. CONCLUSION: Results indicated that suppression of pro-inflammatory enzymes/cytokines, inhibition of protein denaturation, lysosomal membrane stabilizing abilities, and redox/free radical scavenging properties of RO extract and fractions support anti-arthritic and immunomodulatory property of Ribes orientale that might be due to its polyphenolic and flavonoid constituents. This suggests that Ribes orientale roots may be used as a therapeutic agent for treating human arthritis.

Amelioration of adjuvant induced arthritis in Sprague Dawley rats through modulation of inflammatory mediators by Ribes alpestre Decne.

ETHNOPHARMACOLOGICAL RELEVANCE: Ribes alpestre Decne has been commonly used in the treatment of joint complaints. AIM OF STUDY: The present study was undertaken to evaluate the antiarthritic potential of ethanolic extract and fractions of Ribes alpestre and to explore its probable mechanism of action. MATERIAL AND METHODS: Complete Freunds adjuvant induced arthritis in Sprague Dawley rats was used to assess antiarthritic activity of aqueous ethanol extract, butanol and aqueous fractions at 200 mg/kg oral dose for 28 days. Paw volume and diameter, arthritic index, body weight, hematological and biochemical parameters, radiographic and histological analysis of ankle joints were carried out. An array of pro-inflammatory mediators (IL-1ß, IL-6, NF-Kß, TNF-α, COX-2, IL-4, IL-10 and PGE2) were estimated by RT-PCR and enzyme linked immunosorbent assay. Antioxidant capacity was assessed using DPPH and reducing power assays. Qualitative phytochemical screening, total phenolic and flavonoid content and HPLC analysis of aqueous fraction of Ribes alpestre were also carried out. RESULTS: Significant (p < 0.001) reduction in paw volume and thickness and arthritic score by aqueous ethanolic extract and its fractions has been found. Aqueous ethanolic extract and fractions in particular aqueous fraction considerably prevented decrease in body weight, alterations in hematological parameters. Radiographic and histological examination revealed no significant architectural changes in joints of treated rats. Significant (p < 0.05-0.001) down regulation of pro-inflammatory genes IL-1ß, TNF-α, IL-6, COX-2, PGE2 and NF-Kß alongwith noteworthy increase in levels of IL-4 and IL-10 was recorded among treated animals. Aqueous ethanol extract and its fractions demonstrated notable and concentration dependent (50-6400 µg/ml) antioxidant potential. Qualitative phytochemical analysis of active fraction (aqueous) displayed presence of flavonoids, alkaloids, tannins and glycosides. Besides total phenolic and flavonoid contents has been found to be 179.3 mg GAE/ml and 389.40 µg QE/ml in aqueous fraction of Ribes alpestre respectively. HPLC profile demonstrated presence of quercitin, chlorogenic acid, vanillic acid and cinamic acid in aqueous fraction. CONCLUSION: Present communication suggests Ribes alpestre a potent antiarthritic therapy by ameliorating adjuvant arthritis in rats by downregulating proinflammatory mediators with up regulation of anti-inflammatory cytokines.

Inhibitory effects of Clematis orientalis aqueous ethanol extract and fractions on inflammatory markers in complete Freund's adjuvant-induced arthritis in Sprague-Dawley rats.

Clematis orientalis Linn has long been used as ethnopharmacy for the treatment of arthritis. This study is intended to evaluate the curative efficacy of Clematis orientalis in treating polyarthritis in rats. Aqueous ethanolic extract and fractions (hexane, butanol and aqueous) were administered orally at 200 mg/kg for 28 days after CFA immunization. Paw swelling, paw diameter, arthritic score, body weight, hematological parameters, radiographic and histological analysis of ankle joints were evaluated. Moreover, levels of various inflammatory markers through RT-PCR and ELISA were measured. DPPH and reducing power assays were used to appraise antioxidant capacity. Qualitative phytochemical analysis, determination of total phenolic and flavonoid contents were also carried out. Aqueous ethanolic extract and fractions significantly (p < 0.001) reduced paw volume, paw thickness and arthritic score and considerably prevented decrease in body weight along with anomalous alterations in hematological parameters in comparison with arthritic control. X-ray and histological examination revealed no significant structural changes in ankle joints of treated rats. Expression levels of IL-1ß, TNF-α, IL-6, COX-2 and NF-Kß were significantly (p < 0.05-0.001) suppressed as well as noteworthy increase in the levels of IL-4 and IL-10 among treated animals has been detected. Overproduction of TNF-α and PGE2 was substantially prevented in animals given different treatments. Aqueous ethanol extract and its fractions demonstrated significant and concentration-dependent antioxidant potential. In general, among fractions aqueous fraction exhibited a greater anti-arthritic effect. Phytochemical analysis of aqueous fraction confirmed the presence of flavonoids and glycosides, 215.29 mgGAE/ml phenolic content and 633.03 µgQE/ml flavonoid content. Thus, we suggest Clematis orientalis as a potent strategy for the treatment of rheumatoid arthritis.

Indigenous medicinal plants of Pakistan used to treat skin diseases: a review.

ETHNO-PHARMACOLOGICAL RELEVANCE: Plants are providing reliable therapy since time immemorial. Pakistan has a great diversity in medicinal flora and people use these ethno-medicines to deal with many skin problems. This review explores the fundamental knowledge on various dermatological properties of medicinal plants of Pakistan and is aimed to provide a baseline for the discovery of new plants having activities against skin issues. MATERIAL AND METHOD: A total of 244 published articles were studied using different research engines like PubMed, Google, Google-scholar and science direct. RESULTS: Review of literature revealed ethno-pharmacological use of 545 plant species, belonging to 118 families and 355 genera, to combat various skin ailments. Out of these, ten most commonly used plant species belonging to ten different families are documented in this review. It was also found out that ehno-medicines are prepared using various parts of the plants including leaves (28.32%), whole plant and roots 13.17% and 10.97% respectively, in the form of powder (23.5%) and paste (22.75%). A total of 13 endangered plant species and ten commercially important plants were recorded. CONCLUSION: Medicinal plants of Pakistan have therapeutic effects against several skin problems; however most of medicinal plants are still not evaluated scientifically to support their ethno-pharmacological claim on skin. Dermatological pathogens are recommended to study. Further, the conservational programs should be established for endangered species.

Traditional medicinal plants used for respiratory disorders in Pakistan: a review of the ethno-medicinal and pharmacological evidence.

Respiratory disorders are a common cause of malady and demise in Pakistan due to its remoteness, cold and harsh climatic conditions as well as scarce health care facilities. The people rely upon the indigenous plant resources to cure various respiratory disorders. The primary objective of this review was to assemble all available ethno-medicinal data of plants used for respiratory disorders in Pakistan. Pharmacological activity of these plants (based upon published scientific research), distribution, diversity, use, preparation methods, economical value, conservation status and various available herbal products of some plants have also been explored. This study scrutinized various electronic databases for the literature on medicinal plants used in Pakistan to treat respiratory disorders. A total of 384 species belonging to 85 families used to treat respiratory disorders in Pakistan has been documented. Cough was the disorder treated by the highest number of species (214) followed by asthma (150), cold (57) and bronchitis (56). Most of the plants belongs to Asteraceae (32) and Solanaceae family (32) followed by moraceae (17), Poaceae (13), and Amaranthaceae (13) with their habit mostly of herb (219) followed by Shrub (112) and tree (69). Traditional healers in the region mostly prepare ethno medicinal recipes from leaves (24%) and roots (11%) in the form of decoction. Among the reported conservation status of 51 plant species, 5 were endangered, 1 critically endangered, 11 vulnerable, 14 rare, 16 least concern, 3 infrequent and 1 near threatened. We found only 53 plants on which pharmacological studies were conducted and 17 plants being used in herbal products available commercially for respiratory disorders. We showed the diversity and importance of medicinal plants used to treat respiratory disorders in the traditional health care system of Pakistan. As such disorders are still causing several deaths each year, it is of the utmost importance to conduct phytochemical and pharmacological studies on the most promising species. It is also crucial to increase access to traditional medicine, especially in rural areas. Threatened species need special attention for traditional herbal medicine to be exploited sustainably.

Celiac disease presenting as rickets in Saudi children.

BACKGROUND AND OBJECTIVES: Rickets is commonly seen as a sign of malabsorption like celiac disease if it is not treated appropriately with vitamin D and calcium supplements. The aim of this study was to examine the frequency of diagnosis of celiac disease among children with unexplained rickets in Saudi children at a tertiary hospital setting. DESIGN AND SETTING: Retrospective review of records of patients referred over 10 years to a pediatric gastroenterology and hepatology unit. PATIENTS AND METHODS: The study included all patients referred for evaluation of unexplained rickets and osteomalacia and screened for celiac disease. The diagnosis of rickets was made on the basis of history, physical examination, biochemical and radiological investigations. The diagnosis of celiac disease was made based on the ESPGHAN (European Society for Pediatric Gastroenterology, Hepatology, and Nutrition) criteria. RESULTS: Twenty-six children with a mean (SD) age of 9.5 (4.6) years (5 males, range 1-15 years) were referred for evaluation of unexplained rickets and were screened for celiac disease. The diagnosis of celiac disease based on small bowel biopsy findings was confirmed in 10 (38.4%) patients with rickets. Serological markers for celiac disease including antiendomyseal antibodies and antitissue transglutaminase antibodies were positive in all ten children. CONCLUSION: Rickets is not an uncommon presentation of celiac disease in Saudi children and pediatricians should consider celiac disease as an underlying cause for rickets.