Gastroprotective effect of low dose Eugenol in experimental rats against ethanol induced toxicity: Involvement of antiinflammatory and antioxidant mechanism.

ETHNOPHARMACOLOGICAL RELEVANCE: Syzygium aromaticum L. volatile oil (clove oil) has been traditionally used for various stomach disorders including inflammatory conditions. Eugenol is the major constituent present in the volatile oil, and it has been established as a gastroprotective agent through many published studies, but the exact and complete mechanism of ulcer protection is not delineated yet. Moreover, it plays precisely the opposite effect in higher dose in antiulcer properties with worsening the ulcer at a higher dose. AIM: This study aims to carry out the prophylactic cytoprotective effect of eugenol with single low doses and explore the probable interrelated underlying transcriptional and translational level mechanism of cytoprotection such as antioxidative, anti-inflammatory, mucous generation in rats using ethanol-induced ulcer model. METHODS: Rats were administered with different doses of eugenol before ethanol intragastrically. The effects of the eugenol on mucous production, Nitric oxide generation, PGE2 synthesis, lipid peroxidation were recorded together with cytokines measurement in the blood. TNF-α and IL-6, two key cytokines, were also studied in specific. In addition, studies on the immunohistochemical and gene expression of HSP70 and iNOS indicators have been conducted. RESULTS: According to our findings, Eugenol substantially reduced the ulcer index and completely protected the mucosa from lesions. By restoring the lowered GSH and NP-SH levels, the protective effect of the eugenol was found to be augmented at both doses. This finding has corresponded to an increase in MDA, which was lowered by ethanol administration. Pre-treatment with eugenol on the ethanol-induced ulcer reduced the plasma NO levels and increased PGE2 along with a decreased TNF-α and IL-6 concentration. Additionally, significant transcriptional and translational upregulation of HSP70 and downregulation of iNOS were detected in the eugenol-treated rat stomach tissue. CONCLUSION: Our findings demonstrated that eugenol had a considerable gastroprotective impact at low doses, which could be attributed to its ability to regulate inflammatory reactions and antioxidant capacity.

Diagnosis and Causative Species of Visceral Leishmaniasis in Southwest Saudi Arabia.

Visceral leishmaniasis (VL) is the most severe clinical form of the disease and has been reported in the Jazan region of southwest Saudi Arabia. This study aimed to diagnose VL by real-time polymerase chain reaction (PCR) and the direct agglutination test (DAT) and to identify the causative Leishmania species. A total of 80 participants, including 30 suspected VL patients, 30 healthy endemic control individuals, and 20 malaria disease controls, were enrolled in this study. Blood samples were collected and tested for Leishmania DNA by real-time PCR and for antibody by the DAT. Sequencing of some amplified PCR products was used to identify the causative Leishmania species. The diagnosis of VL was successfully achieved by both real-time PCR and by DAT with 100% sensitivity. Leishmania donovani and Leishmania infantum species were detected by sequencing both by the kDNA and ITS1 target genes, followed a BLASTn search. The detection of VL antibody by the DAT followed by the confirmatory detection of Leishmania DNA in patient blood by PCR could promote the adoption of the much less invasive and more sensitive methods for the routine diagnosis of VL. Further study with high sample volume to evaluate the PCR and the DAT are needed, to generate more robust evidence. Based on the sequencing results, emerging studies on VL should focus on the causative Leishmania species, reservoirs, and vectors that are important in the study area.

Kelch 13-propeller polymorphisms in Plasmodium falciparum from Jazan region, southwest Saudi Arabia.

BACKGROUND: Artemisinin-based combination therapy (ACT) is recommended at the initial phase for treatment of Plasmodium falciparum, to reduce morbidity and mortality in all countries where malaria is endemic. Polymorphism in portions of P. falciparum gene encoding kelch (K13)-propeller domains is associated with delayed parasite clearance after ACT. Of about 124 different non-synonymous mutations, 46 have been identified in Southeast Asia (SEA), 62 in sub-Saharan Africa (SSA) and 16 in both the regions. This is the first study designed to analyse the prevalence of polymorphism in the P. falciparum k13-propeller domain in the Jazan region of southwest Saudi Arabia, where malaria is endemic. METHODS: One-hundred and forty P. falciparum samples were collected from Jazan region of southwest Saudi Arabia at three different times: 20 samples in 2011, 40 samples in 2016 and 80 samples in 2020 after the implementation of ACT. Plasmodium falciparum kelch13 (k13) gene DNA was extracted, amplified, sequenced, and analysed using a basic local alignment search tool (BLAST). RESULTS: This study obtained 51 non-synonymous (NS) mutations in three time groups, divided as follows: 6 single nucleotide polymorphisms (SNPs) '11.8%' in samples collected in 2011 only, 3 (5.9%) in 2011and 2016, 5 (9.8%) in 2011 and 2020, 5 (9.8%) in 2016 only, 8 (15.7%) in 2016 and 2020, 14 (27.5%) in 2020 and 10 (19.6%) in all the groups. The BLAST revealed that the 2011 isolates were genetically closer to African isolates (53.3%) than Asian ones (46.7%). Interestingly, this proportion changed completely in 2020, to become closer to Asian isolates (81.6%) than to African ones (18.4%). CONCLUSIONS: Despite the diversity of the identified mutations in the k13-propeller gene, these data did not report widespread artemisinin-resistant polymorphisms in the Jazan region where these samples were collected. Such a process would be expected to increase frequencies of mutations associated with the resistance of ACT.

Whole-Genome Sequencing of a Mycobacterium tuberculosis Strain Belonging to Lineage 1 (Indo-Oceanic) and the East African Indian Spoligotype, Isolated in Jazan, Saudi Arabia.

We describe here the draft genome sequence of AY1MRC, a Mycobacterium tuberculosis strain belonging to lineage 1 (Indo-Oceanic) and the East African Indian spoligotype, isolated from a patient with tuberculosis in Jazan, Saudi Arabia.

Ameliorative effect of Boesenbergin A, a chalcone isolated from Boesenbergia rotunda (Fingerroot) on oxidative stress and inflammation in ethanol-induced gastric ulcer in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Boesenbergia rotunda (L.) Mansf. Kulturpfl., previously known as Boesenbergia pandurata (Family: Zingiberaceae) is a ginger species, locally known as fingerroot. It is an integral part of Southeast Asian traditional medicine in alleviating many gastrointestinal disorders such as flatulence, carminative, stomach ache, dyspepsia, and peptic ulcer. AIM OF THE STUDY: Earlier we have investigated the cytoprotective effect of Boesenbergia rotunda extract. In the present study, we investigated the gastroprotection activity of Boesenbergin A (BA), a chalcone isolated from Boesenbergia rotunda extract in ethanol-induced ulcer model in rats. Besides, the contribution of anti-inflammatory and anti-oxidant ability of BA as probable mechanisms involved in the anti-ulcer activity, also been studied. MATERIALS AND METHODS: BA was orally administered in rats before ulcer induction with ethanol. The lesions of the gastric mucosa were evaluated macroscopically and histopathologically. The efficiency of BA in mucus production, NO production, PGE2 synthesis, mucosal nonprotein sulphydryls, glutathione (GSH) level, and lipid peroxidation (MDA) level were studied. The involvement of the anti-inflammatory capacity of BA was analyzed by using the measurement of cytokines such as TNF-α and IL-6. Finally, the expression of biomarkers such as HSP 70 and iNOS was analyzed at the transcriptional and translational levels. RESULTS: We confirmed the protective capacity of BA via the reduction of ulcerated and haemorrhagic areas. It has induced the protection through lowering GSH, MDA and increased NP-SH level. The plasma NO levels were significantly less in BA treated rats. Both cytokines TNF-α and IL-6 were decreased together with elevated PGE2. Upregulation of HSP and downregulation of iNOS were determined in immunohistochemical and gene expression studies CONCLUSIONS: The current results suggest that the prophylactic effect found with BA is due to (i) boosting of gastric mucus production and suppression of inflammatory mediators, via pro-inflammatory cytokines and (ii) modulating the oxidative stress response. The usefulness of Boesenbergia rotunda in folk medicine in treating ulcers partially could be due to the presence of this chalcone.

Girinimbine from curry leaves promotes gastro protection against ethanol induced peptic ulcers and improves healing via regulation of anti-inflammatory and antioxidant mechanisms.

Curry leaves (Murraya koenigii) are a leafy spice used in Indian cookery for its fragrant aroma. Many bioactive functional compounds have been identified, and among them carbazole alkaloids have attracted wide attention due to their multi-dimensional medicinal value. Even though it has been established that the carbazole alkaloid is responsible for the anti-ulcer effect showed by this culinary herb, there is no further evidence to say which phytochemical is responsible for this. In the present study, we investigated the gastro-protective effects and mechanism of girinimbine, a major carbazole alkaloid present in curry leaves. Rats were administered with ethanol to produce gastric ulcers, and the prophylactic effect of girinimbine was evaluated. A macroscopic and histological examination was carried out to examine the lesions. Furthermore, the mucus production, NO production, PGE2 synthesis, mucosal nonprotein sulphydryls, glutathione (GSH) level, lipid peroxidation (MDA) level and COX inhibition were assessed. In addition, in particular, TNF-α and IL-6, two important cytokines, were evaluated. Immunohistochemical and gene expression studies were conducted to determine the HSP70 and iNOS biomarkers. Our results indicated that girinimbine significantly reduced the ulcer index and totally safeguarded the mucosa from lesions. The protective effect of girinimbine was complemented through the restoration of the reduced GSH and NP-SH level. This was associated with a reduction of MDA, which was elevated by the administration of ethanol. Pre-treatment of the ethanol induced ulcer with girinimbine reduced the NO concentration in the plasma and elevated PGE2 together with a decreased level of TNF-α and IL-6. Girinimbine had shown suppressing effects on COX-2 enzymes, but not on COX-1. In addition, significantly upregulated HSP70 and downregulated iNOS were observed in girinimbine treated rat tissue at both the transcriptional and translational level. Our results clearly indicated that girinimbine displayed a significant gastro-protection effect, via the capacity to inhibit inflammatory responses and antioxidant potential.