Atmospheric pollution contributes to oxidative cellular damage and metabolic disorders due to hepatic metabolism of some toxins. In this study, we evaluated the in vitro antioxidant capacity of Pistacia lentiscus extract. Furthermore, the in vivo anti-inflammatory, antioxidant, and hepatoprotective effects were explored in DMBA-mice model. We also evaluated the systems-level characterization of gene networks associated with environmental response with genes regulated by the AhR/ARNT and HIF-2α/ARNT signaling pathways. Our results proved that P. lentiscus presented a rich source of fatty acids and secondary metabolites. In vitro, it demonstrated a strong free radical scavenging capacity with antioxidant effects. In vivo, DMBA exposure altered lipid profiles and CBCC with C-RP content, induced oxidative stress, and disrupted liver and kidney function. Cotreatment with P. lentiscus corrected plasma biochemical parameters, restored the C-RP activity and CBCC levels (C-RP: 0.9 µg/dL; WBC: 15.6 × 109/L; Mid: 0.22 × 109/L), reduced lipid peroxidation, and enhanced antioxidant enzyme activities (SOD, CAT, GPx; p < 0.05). Histological analysis confirmed the protective effects of P. lentiscus on liver tissue, preventing steatosis and cellular injury. Network analysis highlighted the central role of the AhR/ARNT complex and its molecular partners in coordinating xenobiotic metabolism and cellular adaptive responses, revealing a mechanistic basis for P. lentiscus as a promising anti-inflammatory and antioxidant dietary supplement with potential hepatoprotective effect.

Boscia senegalensis (Pers.) Lam. Ex Poir. (Capparaceae) is an important local famine food plant in Africa and is widely exploited by healers in the Sahelian region for its seeds, which are used to reduce hyperglycemia. We studied the efficacy of the commercial dosage form of Boscia senegalensis, namely Boscisucrophage (BSP), in type 2 diabetes (T2DM) patients with resistance to oral antihyperglycemic drugs. The clinical benefits of BSP were in a prospective, single-center, open-label, single-arm interventional study involving 43 naïve patients and 289 diabetic patients resistant to oral antidiabetic drugs. All patients received capsules containing a fixed dose of 350 mg of BSP, taken three times daily for 12 weeks. Outcomes were monitored through venous blood glucose levels, glycosylated hemoglobin (HbA1c), urine glucose excretion (UGE), aspartate aminotransferase, alanine aminotransferase, creatinine levels, and clinical examination of functional symptoms. In the clinical study, BSP significantly reduced glycemia and HbA1c levels, increased urine glucose excretion (UGE), and alleviated the side effects and functional symptoms of T2DM. Our clinical findings provide preliminary evidence supporting the potential use of BSP to reduce glycemia and HbA1c in T2DM patients resistant to oral antihyperglycemic drugs, with no significant adverse effects observed in this study. These results highlight BSP's potential as a dual SGLT1/SGLT2 inhibitor, suggesting a novel mechanism of action. However, further validation through randomized controlled trials is necessary to confirm these findings. Trial Registration: National Ethics Committee (N°679/PR/PM/MSP/SE/SG/DHATC/SGH/SRH/13).

BACKGROUND:Arbutus and hawthorn fruits are commonly utilized in traditional medicine to address various gastrointestinal (GI) ailments. Our primary aim was to individually assess the effects of aqueous extracts from Arbutus unedo (AUAE) and Crataegus monogyna (CMAE) fruits on GI motility, spontaneous jejunal smooth muscle contractility, and hyperglycemia management. METHODS:Wistar rats were administered loperamide (LOP, 3 mg/kg, b.w.) along with AUAE or CMAE (at doses of 75, 150 and 300 mg/kg, b.w.) or yohimbine (YOH, 2 mg/kg, b.w.). GI transit was evaluated using the charcoal meal test. The impact of both extracts on jejunal secretion and contraction was assessed using the Ussing chamber technique and the isometric transducer. The bioactive constituents of AUAE and CMAE were analyzed via liquid chromatography-high resolution electrospray ionization mass spectrometry (LC-HRESIMS). RESULTS:AUAE and CMAE comprise bioactive compounds, including phenolic acids, flavonoids, and flavonols, capable of eliciting various intended physiological effects. Both extracts demonstrated a significant and dose-dependent increase in GI transit (77.33%-89.83% and 80.31%-85.54%, respectively) compared to the delayed peristalsis induced by LOP (42.77%) and the accelerated effect of YOH (90.09%). Both extracts induced an increase in the amplitude of spontaneous jejunal contraction with an EC50 of 90.47 and 22.98 μg/mL, respectively. Conversely, the two extracts did not impact the electrogenic transport of intestinal fluid when compared to the action produced by forskolin (FSK, 10 μM). Additionally, both extracts significantly reduced glucose levels in hyperglycemic rats compared to control values. CONCLUSION:These findings hold promise for the development of novel preventive and pharmacological treatment strategies for GI disorders and diabetes management.

Background: Nigella sativa L. (seeds) and Olea europaea L. (leaves) are widely utilized as food supplements and traditional herbal remedies to reduce hyperglycemia. Purpose: This study evaluated the efficacy of a commercial combination of Nigella sativa and Olea europaea aqueous extracts, marketed as Phytosucrophage (PSP), in managing type 2 diabetes mellitus (T2DM) in patients resistant to oral antihyperglycemic drugs (OADs). Study Design: A multicenter, observational cohort study was conducted involving 38 treatment-naïve T2DM patients and 282 patients resistant to OADs. Participants received a fixed-dose capsule containing 550 mg of PSP, administered twice daily for 12 weeks. Clinical efficacy was assessed by monitoring fasting blood glucose, glycosylated hemoglobin (HbA1c), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine levels, and evaluating functional symptoms. Results: PSP treatment significantly reduced fasting blood glucose and HbA1c levels. Additionally, it alleviated functional symptoms of T2DM without inducing adverse effects. Conclusions: The findings suggest that PSP is an effective and safe adjunctive therapy for reducing blood glucose and HbA1c levels in T2DM patients resistant to OADs. PSP also improved clinical symptoms associated with T2DM without causing notable adverse effects.

ETHNOPHARMACOLOGICAL RELEVANCE:Olea europaea L. and Hyphaene thebaica L. are commonly employed by traditional healers in Africa for treating and preventing hypertension, either individually or in a polyherbal preparation (Ifanosine).AIM OF THE STUDY:The primary aim was to assess the antihypertensive effects of Olea europaea L. leaves aqueous extract (OEL), Hyphaene thebaica L. mesocarp extract (HT), and the Ifanosine on isolated rat aorta rings. The secondary objective was to evaluate the clinical benefits of a new oral formulation of Ifanosine.MATERIALS AND METHODS:In vitro studies using an isometric transducer examined the antihypertensive effects of HT, OEL, and Ifanosine on rat aorta. Ussing chambers technic were employed to measure mucosal to serosal fluxes and total transepithelial electrical conductance (Gt) to assess the intestinal bioavailability of HT, OEL, and Ifanosine. HPLC was utilized to determine the phytochemical composition of OEL and HT extracts. Subchronic toxicity investigations involved two groups of rats, treated with either water (control) or Ifanosine at 5 g/kg for 28 days. Clinical benefits of the new Ifanosine formulation were evaluated in an observational study with 32 hypertensive patients receiving a fixed oral dose of 3.5 mg three times a day for 30 days.RESULTS:Aqueous extracts induced dose-dependent relaxation of rat aorta rings, with HT and OEL having higher IC50 values than Ifanosine (IC50 = 44.76 ± 1.35 ng/mL, 58.67 ± 1.02 ng/mL, and 29.46 ± 0.26 ng/mL, respectively). The pA2 values of OEL and HT were 1 and 0.6, respectively, while Ifanosine was 0.06. Intestinal bioavailability studies revealed better Prazosin bioavailability than plant extracts. Toxicological studies demonstrated the safety of Ifanosine, supported by histological examinations and biochemical parameters in rat blood. Biochemical analyses indicated flavonoids and phenolic acids as dominant active constituents. Clinical benefits in humans included reduced SBP, DBP, LDL-c, VLDL-c, and TAG, and increased HDL-c without overt adverse effects.CONCLUSION:This study validates the traditional use of OEL and HT for hypertension and advocates for alternative and combinatorial polyphytotherapy (ACP) to enhance traditional remedies.

Background/Objectives: Boscia senegalensis (BS) Pers.) Lam. Ex Poir (Capparaceae), is an important local famine food plant in Africa and widely exploited by healers for its seeds in Sahelian region to reduce hyperglycaemia. Purpose: We studied the efficacy of commercial dosage form of BS namely Boscisucrophage (BSP) on type 2 diabetes (T2DM) patients with Oral antihyperglycemic drugs resistant. Study Design: Clinical benefits of BSP, were evaluated in multicentre cohort observational study on naïve patients (43) or diabetic patients resistant of oral antidiabetic drugs (289). All patients received capsules of the fixed dose containing 350 mg of BSP twice daily for 12 weeks and overactive control on vein blood sugar, glycosylated haemoglobin (HbA1c), urine glucose excretion (UGE), aspartate aminotransferase, alanine aminotransferase, creatinine, and clinical examination of functional symptoms. Results: In clinical study, BSP induced the reduction of glycaemia, HbA1c, and increase UGE, with removal of side effects functional symptoms of T2DM. Conclusions: In clinical studies, our findings lend support to use of BSP to reduce glycaemia, and HbA1c in T2DM patients with Oral antihyperglycemic drugs resistant without over adverse effects. BSP supressed clinical examination of functional symptoms.

Background: The traditional recipe of Cupidon of Pahouins (CP) is an age-old secret kept by the female healers of the Fang people in Central Africa for feminine intimate care. The most widely used formulation is composed of four plant extracts: Alchornea cordifolia (Schumach. & Thonn.) Müll.Arg., Musanga cecropioides R.Br. ex Tedlie, Myrianthus arboreus P.Beauv., and Myrianthus arboreus P.Beauv. Aim of the Study: The first objective of this study was to test the antibacterial, antifungal, and antineoplastic effects of each plant extract alone, and then to test the combination of the most active extracts in a polyherbal formulation (PHF). The secondary objective was to assess the mechanism of action of the PHF. The third objective was to evaluate the clinical benefits of the new formulation (PHF) in a multicenter observational cohort study after the evaluation of side effects. Materials and Methods: Antibacterial and antifungal activities were evaluated using the agar dilution method. Protein synthesis inhibitors were used to target the mechanism of action of CP and its anticancer activity using the seed germination method. The rational formulation of the candidate CP was achieved using the functional approach. Transdermal passage of CP was measured using Franz diffusion chambers. Side effects on skin and eyes were assessed using skin and eye irritation tests. The clinical benefits of CP were evaluated after medical examination in an observational study involving a cohort of 451 patients suffering from different infectious diseases, such as vaginal and oral infections, as well as skin, eye, and ear infections. Results: The plant extracts used in the traditional formulation exhibited antibacterial and antifungal effects. The best results were obtained with Alchornea cordifolia and Musanga cecropioides, which were subsequently combined in a PHF to produce a new CP. On Gram-positive bacteria, CP was most effective against Enterococcus faecalis, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus warneri, Staphylococcus pettenkoferi Staphylococcus agalactiae, as well as Corynebacterium striatum. The same efficacy was observed on Gram-negative bacteria such as Citrobacter freundii, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter aerogenes, Proteus mirabilis, and Salmonella spp. In addition, the effect of CP was synergistic on several microorganisms tested (FICI < 1). The new PHF exhibited antifungal activity against Candida albicans, as well as antineoplastic activity (IC50 = 2.92 ± 0.12 mg/mL). A positive clinical benefit was observed in humans following the use of CP. The phytodrug cleared infections of the skin, ears, eyes, vagina, and mouth, with no obvious adverse effects. Conclusion: This study confirms the efficacy of traditional PHF in treating or preventing bacterial and fungal infections. This study shows that alternative and combination poly-phytotherapy (ACP) can be used to improve the efficacy of traditional treatments.

Background: Boscia senegalensis Pers.) Lam. Ex Poir (Capparaceae) (BS), is an evergreen, perennial woody shrub, or tree native to Sahel region in Africa. It is an important local food plant in Africa and widely exploited for its fruits and seeds. Aim of the Study: The objective of this study was to test the antihyperglycemic effect of BS ex-vivo an in vivo and the mechanism involve in the reduction of blood sugar. Materials and Methods: We studied the antihyperglycemic effect of aqueous extract of seeds of BS. The chemical composition of BS aqueous extract was determined using UHPLC-MS. The inhibition of intestinal glucose absorption was studied ex-vivo in mice using a short-circuit current technique. The antihyperglycemic of BS in vivo was assess using an oral glucose tolerance test (OGTT) in rat. Results: In preclinical studies, BS (5 µg/mL to 2 mg/mL) induced concentration-dependent inhibition of sodium-dependent glucose transport across isolated mouse jejunum. The maximal inhibition was obtained with 2 mg/mL and was represented more than 75 % of the effect of Phloridzine and IC50 was close to 477.53 ± 1.22 µg/mL. Chronic BS treatment improved glucose tolerance and reduced body weight without any toxic effect in rat. The major compound found in the aqueous extract of BS seed was Glucocapparin (methyl glucosinolates). Conclusion: The result shows that BS directly inhibits the intestinal absorption of glucose ex-vivo in mice and it improved glucose tolerance and body weight in rats after acute and chronic oral administration in vivo.

The pervasive presence of atmospheric pollution, particularly polycyclic aromatic hydrocarbons such as 7,12-dimethylbenz(a)anthracene, instigates aberrant cellular and tissue conditions, precipitating oxidative damage and inflammatory cascades conducive to the onset of cancer, notably mammary cancer. Given the hepatic metabolism of 7,12-dimethylbenz(a)anthracene, the imperative of employing natural antioxidants becomes apparent. In this study, we delve into the antioxidant and hepato-protective properties of Pistacia lentiscus against 7,12-dimethylbenz(a)anthracene-induced toxicity, alongside exploring its potential anticancer attributes. Our investigations unveil Pistacia lentiscus's anti-proliferative efficacy against human breast cancer cell lines. Notably, 7,12-dimethylbenz(a)anthracene-intoxication escalates body weight, disrupts lipid profiles, and incites serum oxidative damage. Concurrently, hepatic and renal oxidative stress ensue, accompanied by heightened antioxidant enzyme activity in the 7,12-dimethylbenz(a)anthracene-exposed-group compared to controls (p<0.05). Nonetheless, Pistacia lentiscus co-administration rectifies biochemical imbalances, significantly attenuates oxidative stress aberrations, and augments antioxidant enzyme responses (p<0.05). Importantly, histological analysis evinces Pistacia lentiscus's shielding effect against 7,12-dimethylbenz(a)anthracene induced hepatocyte injury and steatosis. Our findings underscore Pistacia lentiscus's robust anti-proliferative, antioxidant, and hepato-protective capacities, mitigating metabolic disturbances, oxidative stress propagation in liver and kidney functions, and potential histological alterations, thereby impeding 7,12-dimethylbenz(a)anthracene-induced mammary cancer initiation. We posit that Pistacia lentiscus may serve as a prophylactic agent against breast cancer instigated by this carcinogen.

Cruor, the main component responsible for the red color of mammalian blood, contains 90% haemoglobin, a protein considered to be a rich source of bioactive peptides. The aim of the present study is to assess the potential of human hemoglobin as a source of bioactive peptides, compared with bovine hemoglobin, which has been extensively studied in recent years. More specifically, the study focused on the α137–141 fragment of bovine haemoglobin (TSKYR), a small (653 Da) hydrophilic antimicrobial peptide. In this work, the potential of human hemoglobin to contain bioactive peptides was first investigated in silico in comparison with bovine hemoglobin-derived peptides using bioinformatics tools. The blast results showed a high identity, 88% and 85% respectively, indicating a high similarity between the α and β chains. Peptide Cutter software was used to predict cleavage sites during peptide hydrolysis, revealing major conservation in the number and location of cleavage sites between the two species, while highlighting some differences. Some peptides were conserved, notably our target peptide (TSKYR), while others were specific to each species. Secondly, the two types of hemoglobin were subjected to similar enzymatic hydrolysis conditions (23 °C, pH 3.5), which showed that the hydrolysis of human hemoglobin followed the same reaction mechanism as the hydrolysis of bovine hemoglobin, the ‘zipper’ mechanism. Concerning the peptide of interest, α137–141, the RP-UPLC analyses showed that its identification was not affected by the increase in the initial substrate concentration. Its production was rapid, with more than 60% of the total α137–141 peptide production achieved in just 30 min of hydrolysis, reaching peak production at 3 h. Furthermore, increasing the substrate concentration from 1% to 10% (w/v) resulted in a proportional increase in α137–141 production, with a maximum concentration reaching 687.98 ± 75.77 mg·L−1, approximately ten-fold higher than that obtained with a 1% (w/v) concentration. Finally, the results of the UPLC-MS/MS analysis revealed the identification of 217 unique peptides in bovine hemoglobin hydrolysate and 189 unique peptides in human hemoglobin hydrolysate. Of these, 57 peptides were strictly common to both species. This revealed the presence of several bioactive peptides in both cattle and humans. Although some had been known previously, new bioactive peptides were discovered in human hemoglobin, such as four antibacterial peptides (α37–46 PTTKTYFPHF, α36–45 FPTTKTYFPH, α137–141 TSKYR, and α133–141 STVLTSKYR), three opioid peptides (α137–141 TSKYR,β31–40 LVVYPWTQRF,β32–40, VVYPWTQRF), an ACE inhibitor (β129–135 KVVAGVA), an anticancer agent (β33–39 VVYPWTQ), and an antioxidant (α137–141 TSKYR). To the best of our knowledge, these peptides have never been found in human hemoglobin before.

This study focuses on the enzymatic hydrolysis of hemoglobin, the main component of cruor that gives blood its red color in mammals. The antibacterial and antioxidant potential of human hemoglobin hydrolysates were evaluated in comparison to bovine hemoglobin. The results showed strong antimicrobial activity of the peptide hydrolysates against six bacterial strains, independent of the initial substrate concentration level. The hydrolysates also showed strong antioxidant activity measured by four different tests. In addition, the antimicrobial and antioxidant activity of the human and bovine hemoglobin hydrolysates showed little or no significant difference, with only the concentration level being the determining factor in their activity. The results of the mass spectrometry study showed the presence of a number of bioactive peptides, the majority of which have characteristics similar to those mentioned in the literature. New bioactive peptides were also identified in human hemoglobin, such as antibacterial peptides PTTKTYFPHF (α37-46), FPTTKTYFPH (α36-45), TSKYR (α137-141) and STVLTSKYR (α133-141), as well as an antioxidant TSKYR (α137-141). According to these findings, human hemoglobin represents a promising source of bioactive peptides beneficial to the food or pharmaceutical industries.

Backgrounds: Protein biosynthesis takes place in the ribosome. Some antibiotic and antitumor molecules show more reactivity and affinity with ribosome proteins. These observations encourage the search for protein synthesis inhibitors of targets in the fight against infectious diseases and cancer. This study assessed the utilization of Lepidium sativum (LS) seeds germination in rapidly screening new anticancer candidates for drugs.Methods: Antineoplastic prescribed in the clinic was used at different concentrations in the medium of LS seed germination, and the rootlet length was measured after 72 hours.Results: The results showed that antineoplastics inhibitors of protein synthesis inhibit the germination of seed rootlets whatever their origin: chemicals (R2 = 0.99), antibiotics (R2 = 0.87), or extracts of medicinal plants (R2 = 0.93). The half maximal inhibitory concentration (IC50) obtained was close to that of cancer cell lines. Conclusion: To our knowledge. This is the first demonstration that utilization of seed germination of LS might be used for the rapid screening of new antineoplastics candidates.

Enzymatic hydrolysis of bovine and human hemoglobin generates a diversity of bioactive peptides, mainly recognized for their antimicrobial properties. However, antimicrobial peptides stand out for their ability to specifically target cancer cells while preserving rapidly proliferating healthy cells. This study focuses on the production of bioactive peptides from hemoglobin and evaluates their anticancer potential using two distinct approaches. The first approach is based on the use of a rapid screening method aimed at blocking host cell protein synthesis to evaluate candidate anticancer peptides, using Lepidium sativum seed germination as an indicator. The results show that: (1) The degree of hydrolysis (DH) significantly influences the production of bioactive peptides. DH levels of 3 to 10% produce a considerably stronger inhibition of radicle growth than DH 0 (the native form of hemoglobin), with an intensity three to four times greater. (2) Certain peptide fractions of bovine hemoglobin have a higher activity than those of human hemoglobin. (3) The structural characteristics of peptides (random coil or alpha helix) play a crucial role in the biological effects observed. (4) The α137–141 peptide, the target of the study, was the most active of the fractions obtained from bovine hemoglobin (IC50 = 29 ± 1 µg/mL) and human hemoglobin (IC50 = 48 ± 2 µg/mL), proving to be 10 to 15 times more potent than the other hemoglobin fractions, attributed to its strong antimicrobial potential. The second approach to assessing anticancer activity is based on the preliminary in vitro analysis of hydrolysates and their peptide fractions, with a focus on the eL42 protein. This protein is of major interest due to its overexpression in all cancer cells, making it an attractive potential target for the development of anticancer molecules. With this in mind, astudy was undertaken using a method for labeling formylase (formyl-methionyl-tRNA transformylase (FMTS)) with oxidized tRNA. This approach was chosen because of the similarities in the interaction between formylase and the eL42 protein with oxidized tRNA. The results obtained not only confirmed the previous conclusions but also reinforced the hypothesis that the inhibition of protein synthesis plays a key role in the anticancer mechanism of these peptides. Indeed, the data suggest that samples containing α137–141 peptide (NKT) and total hydrolysates may have modulatory effects on the interaction between FMTS and oxidized tRNA. This observation highlights the possibility that the latter could influence molecular binding mechanisms, potentially resulting in a competitive situation where the ability of substrate tRNA to bind efficiently to ribosomal protein is compromised in their presence. Ultimately, these results suggest the feasibility of obtaining candidate peptides for biological anticancer drugs from both human and bovine hemoglobin sources. These scientific advances show new hope in the fight against cancer, which affects a large number of people around the world.

This study focuses on the enzymatic hydrolysis of hemoglobin, the main component of cruor that gives blood its red color in mammals. The antibacterial and antioxidant potentials of human hemoglobin hydrolysates were evaluated in comparison to bovine hemoglobin. The results showed strong antimicrobial activity of the peptide hydrolysates against six bacterial strains, independent of the initial substrate concentration level. The hydrolysates also showed strong antioxidant activity, as measured by four different tests. In addition, the antimicrobial and antioxidant activities of the human and bovine hemoglobin hydrolysates showed little or no significant difference, with only the concentration level being the determining factor in their activity. The results of the mass spectrometry study showed the presence of a number of bioactive peptides, the majority of which have characteristics similar to those mentioned in the literature. New bioactive peptides were also identified in human hemoglobin, such as the antibacterial peptides PTTKTYFPHF (α37-46), FPTTKTYFPH (α36-45), TSKYR (α137-141), and STVLTSKYR (α133-141), as well as the antioxidant TSKYR (α137-141). According to these findings, human hemoglobin represents a promising source of bioactive peptides beneficial to the food or pharmaceutical industries.

Ginger ( Zingiber officinale ) rhizomes are commonly used in foods and employed for many ailments including gastrointestinal disorders. Our main objective was to evaluate the effect of Zingiber officinale aqueous extract (ZOAE) on gastrointestinal (GI) physiological motility and colonic dysmotility. Thereby, Wistar rats were given loperamide (LP, 3 mg/kg, b.w.) and ZOAE (75, 150, and 300 mg/kg, b.w.) or yohimbine (YOH, 2 mg/kg, b.w.). ZOAE-action on intestinal secretion was assessed using Ussing chamber technique and intestinal motility with isometric transducer. GI-transit (GIT) and gastric emptying (GE) were evaluated with the charcoal meal test and the red phenol methods. ZOAE-bioactive components were analyzed by liquid chromatography-high resolution electrospray ionization mass spectrometry (LC-HRESIMS). Constipation was induced with LP and the different indicators such as stool composition, GIT, oxidative stress biological parameters, and colonic mucosa histological alteration were performed. Anti-constipation effect of ZOAE was confirmed on stool composition, GIT (53.42% to 85.57%), GE (55.47% to 98.88%), and re-established oxidative balance. ZOAE induces an amplitude increase of spontaneous intestinal contraction with EC50 of 10.52 μg/mL. No effect of ZOAE was observed on electrogenic transport of intestinal fluid. These findings suggest that ZOAE-bioactive candidates might exert an anti-constipation action and spontaneous intestinal contraction modulation.

Lavender aqueous extracts are widely used in the Moroccan traditional medicine for their antibacterial properties. However, previous research have generally focused on investigating the antibacterial activity of lavender essential oils. The aim of this study is to evaluate the antibacterial activity of the Moroccan Lavandula pedunculata (Mill.) Cav. aqueous extract, alone, as well as in combination with extracts of other plant species known for their antibacterial activity: Salvia rosmarinus Spenn., Salvia lavandulifolia Vahl. and Origanum compactum Benth. We have tested the antibacterial activity of L. pedunculata, S. rosmarinus, S. lavandulifolia and O. compactum aqueous extracts individually and in combination against 34 strains using the agar dilution method. The combination effect was evaluated using the fractional inhibitory concentration (FIC). Polyphenol and tannin contents were determined using Folin-Ciocalteu reagent, and then some phenolic compounds were identified using UHPLC-MS. All the extracts displayed a large spectrum of antibacterial activity, especially against staphylococci, streptococci, Mycobacterium smegmatis and Proteus mirabilis. The minimum inhibitory concentration (MIC) values reached 0.15 ± 0.00 mg/mL for Staphylococcus warneri tested with S. lavandulifolia and 0.20 ± 0.07 mg/mL for Staphylococcus epidermidis tested with L. pedunculata or S. rosmarinus. Association of the L. pedunculata extract with S. rosmarinus, S. lavandulifolia and O. compactum showed synergistic effects (FIC ≤ 1). Moreover, the association of L. pedunculata with S. lavandulifolia was active against most of the Gram-negative strains resistant to the individual extracts. Determination of polyphenol and tannin contents showed the richness of the studied plants in these compounds. Additionally, chromatographic analysis demonstrated the high presence of rosmarinic acid in all the studied plant extracts. To our knowledge, this is the first study that shows the enhancing effect of the antibacterial activity of L. pedunculata aqueous extract combined with S. rosmarinus, S. lavandulifolia and O. compactum. These results confirm the effectiveness of the plant mixtures commonly used by traditional healers in Morocco and suggest that L. pedunculata might be used as an antibacterial agent either alone or, more efficiently, in combination with S. rosmarinus, S. lavandulifolia and O. compactum.

Ginger ( Zingiber officinale) rhizomes are commonly used in foods and employed for many ailments including gastrointestinal disorders. Our main objective was to evaluate the effect of Zingiber officinale aqueous extract (ZOAE) on gastrointestinal (GI) physiological motility and colonic dysmotility. Thereby, Wistar rats were given loperamide (LP, 3 mg/kg, b.w.) and ZOAE (75, 150, and 300 mg/kg, b.w.) or yohimbine (YOH, 2 mg/kg, b.w.). ZOAE-action on intestinal secretion was assessed using Ussing chamber technique and intestinal motility with isometric transducer. GI-transit (GIT) and gastric emptying (GE) were evaluated with the charcoal meal test and the red phenol methods. ZOAE-bioactive components were analyzed by liquid chromatography-high resolution electrospray ionization mass spectrometry (LC-HRESIMS). Constipation was induced with LP and the different indicators such as stool composition, GIT, oxidative stress biological parameters, and colonic mucosa histological alteration were performed. Anti-constipation effect of ZOAE was confirmed on stool composition, GIT (53.42% to 85.57%), GE (55.47% to 98.88%), and re-established oxidative balance. ZOAE induces an amplitude increase of spontaneous intestinal contraction with EC50 of 10.52 μg/mL. No effect of ZOAE was observed on electrogenic transport of intestinal fluid. These findings suggest that ZOAE-bioactive candidates might exert an anti-constipation action and spontaneous intestinal contraction modulation.

Ginger ( Zingiber officinale ) rhizomes are commonly used in foods and employed for many ailments including gastrointestinal disorders. Our main objective was to evaluate the effect of Zingiber officinale aqueous extract (ZOAE) on gastrointestinal (GI) physiological motility and colonic dysmotility. Thereby, Wistar rats were given loperamide (LP, 3 mg/kg, b.w.) and ZOAE (75, 150, and 300 mg/kg, b.w.) or yohimbine (YOH, 2 mg/kg, b.w.). ZOAE-action on intestinal secretion was assessed using Ussing chamber technique and intestinal motility with isometric transducer. GI-transit (GIT) and gastric emptying (GE) were evaluated with the charcoal meal test and the red phenol methods. ZOAE-bioactive components were analyzed by liquid chromatography-high resolution electrospray ionization mass spectrometry (LC-HRESIMS). Constipation was induced with LP and the different indicators such as stool composition, GIT, oxidative stress biological parameters, and colonic mucosa histological alteration were performed. Anti-constipation effect of ZOAE was confirmed on stool composition, GIT (53.42% to 85.57%), GE (55.47% to 98.88%), and re-established oxidative balance. ZOAE induces an amplitude increase of spontaneous intestinal contraction with EC50 of 10.52 μg/mL. No effect of ZOAE was observed on electrogenic transport of intestinal fluid. These findings suggest that ZOAE-bioactive candidates might exert an anti-constipation action and spontaneous intestinal contraction modulation. Keywords ginger rhizomes , colonic dysmotility , spontaneous intestinal contraction , rats , , , gastro-intestinal transit , antioxidant activity , intestinal contraction

Objectives. - Drug-induced hypersalivation is a frequent drug adverse event of psychotropic drugs. This excess salivary pooling in the mouth can cause an impairment of a patient's quality of life leading to low rates of medication adherence. The optimal management of hypersalivation is thus crucial to improve patient care. To date, no recommendations for limiting drug-induced hypersalivation have been publi-shed. In this study, we conducted a systematic review to investigate the effectiveness of interventions aimed at reducing drug-induced hypersalivation. Methods. - Treatment of drug-induced sialorrhea based on case reports and clinical studies were sought in May 2021 from PubMed, Google Scholar and Science Direct (keywords : ' treatment >>, ' hypersalivation >>, ' induced >>, ' drug >>, ' clozapine >>). Articles published between 1966 to May 2021 on the treatment of drug-induced hypersalivation were included in this study.Results. - Sixty-seven articles were selected in this narrative review. First, patient education associated with non-drug related management are essential to improve the compliance to drugs inducing hyper -salivation. The non-drug related management should be initiated with an increase in the frequency of swallowing with chewing gum. In the case of ineffectiveness, the dosage of drug responsive of sialorrhea can be adjusted according to the patient's response and his/her medical history (i.e. reducing the dose or splitting the daily dose). Finally, if the problem persists, a symptomatic treatment can be added according to the type of sialorrhea (diurnal or nocturnal), preferred galenic by patient, tolerance and availability of drugs. Several drugs have been tested to reduce hypersalivation induced by clozapine (61/67), risperi-done (3/67), quetiapine (2/67) and aripiprazole (2/67). Among the 63 articles targeting a specific corrective treatment, anticholinergic agents were most described in the literature (41 cases out of 63) with atropine, glycopyrrolate and scopolamine (6/41 each). Other agents were described as clinically effective on hyper -salivation: dopamine antagonists (9/63) with amisulpride (5/9), alpha-2-adrenergic agonists (5/63) with clonidine (3/5), botulinic toxin (4/63), and terazosine, moclobemide, bupropion and N-acetylcysteine (for each 1/63). Conclusions. - In the case of drug-induced hypersalivation, after failure of non-drug therapies and dosage optimization of the causative treatment, an anticholinergic drug can be initiated. In case of insufficient res-ponse, the different treatments presented can be used depending on the galenic form, tolerance and access to those medications. The assessment of the risk-benefit balance should be systematic. The heterogeneity of the studies, the little knowledge about the pharmacological mechanism of saliva flow modulation and the unavailability of corrective drugs are different factors contributing to the complexity of therapeutic optimization. (c) 2022 L'Encephale, Paris.

Drug-induced hypersalivation is a frequent drug adverse event of psychotropic drugs. This excess salivary pooling in the mouth can cause an impairment of a patient's quality of life leading to low rates of medication adherence. The optimal management of hypersalivation is thus crucial to improve patient care. To date, no recommendations for limiting drug-induced hypersalivation have been published. In this study, we conducted a systematic review to investigate the effectiveness of interventions aimed at reducing drug-induced hypersalivation.Treatment of drug-induced sialorrhea based on case reports and clinical studies were sought in May 2021 from PubMed, Google Scholar and Science Direct (keywords : « treatment », « hypersalivation », « induced », « drug », « clozapine »). Articles published between 1966 to May 2021 on the treatment of drug-induced hypersalivation were included in this study.Sixty-seven articles were selected in this narrative review. First, patient education associated with non-drug related management are essential to improve the compliance to drugs inducing hypersalivation. The non-drug related management should be initiated with an increase in the frequency of swallowing with chewing gum. In the case of ineffectiveness, the dosage of drug responsive of sialorrhea can be adjusted according to the patient's response and his/her medical history (i.e. reducing the dose or splitting the daily dose). Finally, if the problem persists, a symptomatic treatment can be added according to the type of sialorrhea (diurnal or nocturnal), preferred galenic by patient, tolerance and availability of drugs. Several drugs have been tested to reduce hypersalivation induced by clozapine (61/67), risperidone (3/67), quetiapine (2/67) and aripiprazole (2/67). Among the 63 articles targeting a specific corrective treatment, anticholinergic agents were most described in the literature (41 cases out of 63) with atropine, glycopyrrolate and scopolamine (6/41 each). Other agents were described as clinically effective on hypersalivation: dopamine antagonists (9/63) with amisulpride (5/9), alpha-2-adrenergic agonists (5/63) with clonidine (3/5), botulinic toxin (4/63), and terazosine, moclobemide, bupropion and N-acetylcysteine (for each 1/63).In the case of drug-induced hypersalivation, after failure of non-drug therapies and dosage optimization of the causative treatment, an anticholinergic drug can be initiated. In case of insufficient response, the different treatments presented can be used depending on the galenic form, tolerance and access to those medications. The assessment of the risk-benefit balance should be systematic. The heterogeneity of the studies, the little knowledge about the pharmacological mechanism of saliva flow modulation and the unavailability of corrective drugs are different factors contributing to the complexity of therapeutic optimization.