A review of the safety profile, antioxidant, anti-inflammatory, and bronchorelaxant activities of Waltheria indica Linn (Malvaceae): A potential antiasthmatic phytomedicine.

Introduction: Waltheria indica Linn (Malvaceae) is a widely distributed plant in West Africa. It is commonly used in Burkina Faso to treat inflammation-related diseases, including asthma. Previous reviews have focused on the ethnobotanical, traditional uses, phytochemistry, and pharmacological properties of Waltheria indica. This report aims to compile the biological and pharmacological activities that highlight the anti-asthmatic properties of Waltheria indica L. (W. indica). Method: Electronic databases, such as PubMed, Scopus, Hinari, SciFinder, Google Scholar, and ScienceDirect, were used to gather data on Watheria indica. Data on the toxicological, anti-inflammatory, antioxidant, and bronchorelaxant effects of W. indica were collected. Results: Twenty-three studies describing the biological and pharmacological activities relevant to assessing the anti-asthmatic properties of W. indica were found. Nine articles investigated the anti-inflammatory effects, and three manuscripts were found to have bronchorelaxant activity. Five publications reported the antioxidant activity of the plant extracts. Research on the extracts revealed a tolerable safety profile in rats and mice with an LD50 ranging from 300 to 5000 mg/kg body weight, depending on the parts of the plant used. Phenolic compounds, particularly flavonoids, alkaloids, and saponins, were found to be responsible for the activities involved in the assessment of anti-asthmatic properties. Conclusion: The results of this review suggest that W. indica could be a valuable resource for the treatment of asthma and other respiratory diseases. However, further chemical and pharmacological investigations are needed to understand its mechanism of action in treating asthma.

The Potential of Cochlospermum tinctorium, Flueggea virosa, and Waltheria indica Traditional Plants From Burkina Faso in Treating Periodontitis: A Systematic Review.

Periodontitis is a chronic, infectious, and inflammatory oral disease with a high prevalence in developing countries, where limited access to modern dental care curtails its treatment. This review is dedicated to examining three indigenous botanical species frequently recommended by traditional therapists for the treatment of periodontal disease, namely, Cochlospermum tinctorium, Flueggea virosa, and Waltheria indica, with the aim of elucidating their chemical constituents and pharmacological properties that may support their empirical use. This review adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines extension for scoping reviews. An electronic search was conducted in three databases (PubMed, Science Direct, and Google Scholar) up to July 2022. Out of 700 articles initially identified, only 11 were deemed eligible for inclusion; a substantial majority (80%) of these comprised in vitro studies. Among the trio of botanicals considered, Waltheria indica emerged as the most extensively investigated (65% of the studies). The administration of these plants was predominantly in the form of decoctions or macerations, with extraction methods employing alcoholic agents (ethanolic and methanolic), hydroalcoholic solutions, or aqueous solvents. The selected plants exhibited notable richness in polyphenolic compounds, particularly flavonoids, and demonstrated anti-inflammatory effects, as indicated in 60% of the studies, along with antibacterial properties (against Streptococcus aureus and Helicobacter pylori). None of the studies reported antibacterial activity against periodontal pathogens. The pharmacological properties of these plants may hold promise for the management of oral inflammatory and infectious conditions. Nevertheless, further comprehensive investigations are imperative to establish their safety and efficacy for periodontitis treatment before conclusive recommendations can be formulated.

Antiulcer Effect of Aqueous Ethanolic Extracts of Pseudocedrela kotschyi (Schweinf) Harms (Meliaceae) and Ximenia americana L. (Olacaceae).

Purpose: This study aimed to provide pharmacological evidence of Pseudocedrela kotschyi and Ximenia americana in preventing or healing peptic ulcers claimed by traditional healers in Burkina Faso. Methods: The trunk bark of Pseudocedrela kotschyi and the roots bark of Ximenia americana (Olacaceae) were macerated in mixed ethanol/water (80:20), respectively, to obtain dried extracts. Two models of hydrochloric acid (HCl, 0.3 M/ethanol, 60%) and hypothermic stress-induced peptic ulcer were used. The cytoprotective effect of individual or combined plant extracts was assessed at 1; 10; 30mg/kg. bw. Then, the healing effect of the extracts at 10mg/kg.bw was evaluated within 21 days of treatment on the hydrochloric acid-induced ulcer model. The extracts' antioxidant activity and phenolic content were assessed to support the plant extracts' efficiency. Results: The extracts of P. kotschyi and X. americana at 10 mg/kg.bw reduced ulceration index in hydrochloric acid- and hypothermic stress-ulcer models by more than 83% and 65%, respectively. The extract from X. americana at 10mg/kg.bw allowed complete ulcer healing but not the association of the two plant extracts. The plant extracts had IC50of inhibition of DPPH radical lower than 5µg/mL and total ferric reducing antioxidant power of more than 77 mg EQAA/100mg. The total polyphenolic content was 64.82 ±0.99 and 53.75 ±1.39 mg EGA/g of dried extract of P. kotschyi and X. americana, respectively. Conclusion: X. americana extract is better than the combined two plant extracts in gastric cytoprotection and ulcer healing. Further investigations are needed to highlight mechanism-based effects.

Polyphenolic and Methylxanthine Bioaccessibility of Cocoa Bean Shell Functional Biscuits: Metabolomics Approach and Intestinal Permeability through Caco-2 Cell Models.

Cocoa bean shell (CBS), a by-product with considerable concentrations of bioactive compounds and proven biofunctional potential, has been demonstrated to be a suitable ingredient for high-fiber functional biscuits adapted to diabetic consumers. In this work, the in vitro bioaccessibility and intestinal absorption of polyphenols and methylxanthines contained in these biscuits were evaluated, and the effect of the food matrix was studied. Biscuits containing CBS and the CBS alone underwent in vitro digestion followed by an intestinal permeability study. The results confirmed that compounds were less bioavailable in the presence of a food matrix, although the digestion contributed to their release from this matrix, increasing the concentrations available at the intestinal level and making them capable of promoting antioxidant and antidiabetic activities. After digestion, CBS biscuits were shown to possess α-glucosidase inhibition capacity comparable to that of acarbose. Moreover, the presence of the food matrix improved the stability of polyphenols throughout the digestion process. Intestinal absorption of flavan-3-ols seemed to be limited to a maximum threshold and was therefore independent of the sample, while procyanidin was not absorbed. Methylxanthine absorption was high and was boosted by the presence of the food matrix. The results confirmed the biofunctional potential of CBS-based biscuits.

Characterization of cytotoxic effects of aristolochic acids on the vascular endothelium.

Aristolochic acid nephropathy (AAN) is characterized by interstitial fibrosis, proximal tubular atrophy, and hypoxia. A correlation between a reduced peritubular capillary density and the severity of fibrosis has been demonstrated. As calcium, redox and energetic homeostasis are crucial in maintaining endothelial cell function and survival, we aimed to investigate AA-induced disturbances involved in endothelial cell injury. Our results showed a cytotoxic effect of AA on EAhy926 endothelial cells. Exposure of aortic rings to AA impaired vascular relaxation to Acetylcholine (ACh). Increased levels of intracellular reactive oxygen species (ROS) were observed in cells exposed to AA. Pre-treatment with antioxidant N-acetyl cysteine inhibited AA-induced cell death. Superoxide dismutase resulted in restoring ACh-induced relaxation. An increase in intracellular calcium level ([Ca2+]i) was observed on endothelial cells. Calcium chelators BAPTA-AM or APB, a specific inhibitor of IP3R, improved cell viability. Moreover, AA exposure led to reduced AMP-activated protein kinase (AMPK) expression. AICAR, an activator of AMPK, improved the viability of AA-intoxicated cells and inhibited the rise of cytosolic [Ca2+]i levels. This study provides evidence that AA exposure increases ROS generation, disrupts calcium homeostasis and decreases AMPK activity. It also suggests that significant damage observed in endothelial cells may enhance microcirculation defects, worsening hypoxia and tubulointerstitial lesions.

The ellagitannin metabolite urolithin C is a glucose-dependent regulator of insulin secretion through activation of L-type calcium channels.

BACKGROUND AND PURPOSE: The pharmacology of polyphenol metabolites on beta-cell function is largely undetermined. We sought to identify polyphenol metabolites that enhance the insulin-secreting function of beta-cells and to explore the underlying mechanisms. EXPERIMENTAL APPROACH: INS-1 beta-cells and rat isolated islets of Langerhans or perfused pancreas preparations were used for insulin secretion experiments. Molecular modelling, intracellular Ca2+ monitoring, and whole-cell patch-clamp recordings were used for mechanistic studies. KEY RESULTS: Among a set of polyphenol metabolites, we found that exposure of INS-1 beta-cells to urolithins A and C enhanced glucose-stimulated insulin secretion. We further characterized the activity of urolithin C and its pharmacological mechanism. Urolithin C glucose-dependently enhanced insulin secretion in isolated islets of Langerhans and perfused pancreas preparations. In the latter, enhancement was reversible when glucose was lowered from a stimulating to a non-stimulating concentration. Molecular modelling suggested that urolithin C could dock into the Cav 1.2 L-type Ca2+ channel. Calcium monitoring indicated that urolithin C had no effect on basal intracellular Ca2+ but enhanced depolarization-induced increase in intracellular Ca2+ in INS-1 cells and dispersed cells isolated from islets. Electrophysiology studies indicated that urolithin C dose-dependently enhanced the L-type Ca2+ current for levels of depolarization above threshold and shifted its voltage-dependent activation towards more negative potentials in INS-1 cells. CONCLUSION AND IMPLICATIONS: Urolithin C is a glucose-dependent activator of insulin secretion acting by facilitating L-type Ca2+ channel opening and Ca2+ influx into pancreatic beta-cells. Our work paves the way for the design of polyphenol metabolite-inspired compounds aimed at ameliorating beta-cell function.

Antioxidant activity of crude ethanolic extract and fractions of Ziziphus mauritiana Lam. (Rhamnaceae) leaves from Burkina Faso.

Background Ziziphus mauritiana Lam. is a plant used in traditional medicine in Burkina Faso in the treatment of several diseases, of which diabetes is characterized by oxidative stress. The aim of this study was to evaluate the in vitro antioxidant potential of the extracts of leaves of this plant. Methods The crude hydroethanolic extract (HEE) of the leaves of Z. mauritiana and their partitionates in n-hexane, dichloromethane, and ethyl acetate, and in the residual aqueous solution (the F1, F2, F3, and F4 fractions, respectively) were first prepared. The content of polyphenols was determined and the antioxidant effects of the extracts were evaluated by their 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging activity, inhibition of lipid peroxidation (TBARS), and the ferric reducing antioxidant power (FRAP). Results The HEE as well as the F3 and F4 fractions were rich in polyphenols with contents between 58 and 84 mg equivalent gallic acid per 100 mg. The flavonoid content was 4 mg quercetin equivalents in the HEE and the F4 fraction. Except for the F1 fraction, the HEE and the other fractions showed significant DPPH scavenging activity (IC50 between 8 and 12 µg/mL). The IC50 of TBARS by different extracts was in the range 1-5 µg/mL, and the FRAP activity was 7-85 mg ascorbic acid equivalent per 100 mg. Total polyphenol content was highly correlated with the antioxidant activities. Conclusions The HEE, F3, and F4 fractions were found to be the richest in polyphenols and had the best antioxidant activity. The antioxidant activity of the extracts of the leaves of Z. mauritiana is due to these polyphenolic compounds.

[Prevalence and adverse effects of antihypertensive agents in patients followed up on an ambulatory basis at the University Hospital Yalgado Ouédraogo]. / Prévalence et caractéristiques des effets indésirables des antihypertenseurs chez les patients suivis en ambulatoire au Centre Hospitalier Universitaire Yalgado Ouédraogo.

Medicinal treatment of arterial hypertension (AH) may cause adverse effects which can be annoying and thus influence patient's compliance with treatment. Our study focused on these undesirable effects in patients followed up for AH on an ambulatory basis in the Department of Cardiology at the University Hospital Yalgado Ouédraogo from July to September 2015. Our aim was to determine their rates and their characteristics. Data were obtained from patients' interview, from the examination of patients' follow-up records and of medical consultation forms. A total of 278 patients were included in the study, 69.1% of them were women. The average age was 52.2 ranging between 23 and 86 years; 87.8% of patients lived in urban areas. Smoking, dyslipidemia and a family history of AH accounted for 9%, 35.6% and 57.2% of cases respectively. From a therapeutic perspective, 43.2% of patients were under monotherapy, 35.6% under bitherapy at the start of treatment. Calcium channel blockers (59.7%) were the most used therapeutic drugs. The overall incidence of adverse effects was 60.1%. Calcium channel blockers were involved in 53.6% of adverse events of patients, diuretics in 48.6%. Molecule-specific prevalence was 28.1% for the amlodipine and 24.5% for the hydrochlorothiazide. Excessive diuresis (13.7%), cough (12.9%) and vertigo (11.5%) were the most frequent adverse events reported by the patients. The central and peripheral nervous system and the osteo-muscular system were the most affected systems. Adverse effects are a major determinant of patient's compliance with antihypertensive treatments, because they may have a significant impact on patient's daily life.

MAP Kinase cross talks in oxidative stress-induced impairment of insulin secretion. Involvement in the protective activity of quercetin.

Insulin secretion preservation is a major issue for the prevention or treatment of type 2 diabetes. We previously showed on ß-cells that quercetin (Q), but not resveratrol (R) or N-acetyl cysteine (NAC), amplified glucose-induced insulin secretion in a calcium- and ERK1/2-dependent manner. Quercetin, but not resveratrol or NAC, also protected ß-cell function and hyperamplified ERK1/2 phosphorylation in oxidative stress conditions. As quercetin may interfere with other stress-activated protein kinases (JNK and p38 MAPK), we further explored MAPK cross talks and their relationships with the mechanism of the protective effect of quercetin against oxidative stress. In INS-1 insulin-secreting ß-cells, using pharmacological inhibitors of MAPK pathways, we found that under oxidative stress (50 µm H2O2) and glucose-stimulating insulin secretion conditions: (i) p38 MAPK phosphorylation was increased and regulated by ERK1/2 (positively) and JNK (negatively), although p38 MAPK activation did not seem to play any significant role in oxidative stress-induced insulin secretion impairment; (ii) the JNK pathway appeared to inhibit both ERK1/2 activation and insulin secretion, although JNK phosphorylation was not significantly changed in our experimental conditions; (iii) the functionality of ß-cell in the presence of oxidative stress was closely linked to the level of ERK1/2 activation, (iv) quercetin, resveratrol, or NAC inhibited H2O2 -induced p38 MAPK phosphorylation. The preservation of ß-cell function against oxidative stress appears dependent on the balance between ERK1/2 and JNK activation. The protecting effect of quercetin appears due to ERK1/2 hyperactivation, possibly induced by L-type calcium channel opening as we recently showed.

Preventive effects of nutritional doses of polyphenolic molecules on cardiac fibrosis associated with metabolic syndrome: involvement of osteopontin and oxidative stress.

We previously showed that grape extracts enriched in different polyphenolic families were similarly able to prevent reactive oxygen species (ROS) production, although having differential effects on various features of metabolic syndrome when administered at a dose of 21 mg/kg to the fructose (60%)-fed rat (a model of metabolic syndrome). In the present work, we analyzed on the same model the effect of pure polyphenolic molecules (catechin, resveratrol, delphinidin, and gallic acid) administered at a dose of 2.1 mg/kg. Delphinidin and gallic acid prevented insulin resistance, while gallic acid prevented the elevation of blood pressure. All molecules prevented cardiac ROS overproduction and NADPH overexpression. We also showed that fructose feeding was associated with cardiac fibrosis (accumulation of collagen I) and expression of osteopontin, a factor induced by ROS and a collagen I expression inducer. Collagen I and osteopontin expressions were prevented by the administration of all polyphenolic molecules. The potential use of polyphenols in the prevention of cardiac fibrosis should be further explored.