Hepatoprotective Effect of Curcumin Nano-Lipid Carrier against Cypermethrin Toxicity by Countering the Oxidative, Inflammatory, and Apoptotic Changes in Wistar Rats.

This study investigated the potential hepatoprotective activity of curcumin-incorporated nano-lipid carrier (Cur-NLC) against cypermethrin (Cyp) toxicity in adult Wistar male rats. All animals in groups III, IV, V, and VI were subjected to Cyp (50 mg/kg) toxicity for 15 days. Three different doses of Cur-NLC (1, 2.5, and 5 mg/kg/day) were administered orally for 10 days. The toxic effects were evaluated considering the increases in serum hepatic biomarkers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total protein and albumin, and lipid peroxidation (LPO), as well as a decrease in antioxidative activity (reduced glutathione (GSH), superoxide dismutase (SOD), and catalase) and the upregulation of inflammatory cytokines (IL-1ß, IL-6, and TNF-α). Immunohistochemistry studies of proteins (NF-κB, Apaf-1, 4-HNE, and Bax) showed enhanced expression, and histopathological examination revealed architectural changes in liver cells, indicating liver toxicity in animals. Toxicity was determined by quantitative and qualitative determinations of DNA fragmentation, which show massive apoptosis with Cyp treatment. The administration of Cur-NLC significantly ameliorates all changes caused by Cyp, such as a decrease in the levels of serum liver markers, an increase in antioxidative parameters, a decrease in expression of inflammatory cytokines (IL-1ß, IL-6, TNF-α, and NF-κB), and apoptosis (caspases-3, 9, Apaf-1, 4-HNE, and Bax), according to calorimetric and immunohistochemistry studies. The smear-like pattern of DNA is ameliorated similarly to the control at a high dose of Cur-NLC. Furthermore, all histopathological changes were reduced to a level close to the control. In conclusion, Cur-NLC could be a potent nutraceutical that exhibits a hepatoprotective effect against Cyp-induced hepatotoxicity in rats.

Study of influence of Catha edulis (Khat) chewing on oral pharmacokinetics of irbesartan in rats using a newly developed HPLC-UV method.

Khat consumers might use a number of drugs for underlying conditions; however the potential drug-herb interaction between khat and other drugs including Irbesartan (IRB) is unknown. The present study was conducted to evaluate the effects of khat chewing on pharmacokinetic profile of IRB, a commonly available antihypertensive agent. The pharmacokinetic profile of orally administered IRB (15.5 mg/kg) with and without pre-administration of khat (12.4 mg/kg) were determined in Sprague-Dawley rats. IRB was estimated in rat plasma samples using a newly developed HPLC method. The chromatographic separation of the drug and internal standard (IS) was performed on a C-18 column (Raptor C-18, 100 mm × 4.6 mm id.; 5 µm) using a mobile phase consisting of 10 mM ammonium acetate buffer (pH 4.0) and acetonitrile in a ratio 60:40 v/v. Acceptable linearity for IRB was recorded at 1 - 12 µg/mL concentration range (R2 > 0.99). Intra-day and inter-day precision (%RSD = 0.44% - 3.27% and 0.39-1.98% respectively) and accuracy (% recovery = 98.3 - 104.3%) in rat plasma was within the acceptable limit according to USFDA guidelines. The AUC0-t was found to be significantly increased in IRB-khat co-administered rats as compared to rats receiving IRB only; whereas, the Tmax (0.5 h) value remained unchanged. Results of this study revealed that the IRB level considerably increased in rat plasma upon co-administration of khat. This might be due to the inhibition of CYP2D9 by khat which is the principal cytochrome P450 isoform responsible for IRB metabolism.

Multidrug resistance, prevalence and phylogenetic analysis of genes encoding class II and III integrons in clinically isolated Escherichia coli.

The present study was conducted to evaluate the susceptibility, multidrug resistance and genetic characteristics of Escherichia coli (E. coli) strains, isolated from clinical samples from Jazan Hospital, Jazan, Saudi Arabia. A total of 95 samples were recruited from wound, urine, stool and blood. The isolates were assessed for their antibiotic susceptibilities and the presence of class II and III integrons was studied using PCR technique. Integron II-positive PCR products were further confirmed using partial sequencing. Ampicillin (84.2%) was found to be the most resistant antibiotic followed by ciprofloxacin (57.9%), gentamicin (56.8%), nalidixic acid (50.5%), cefotaxim (49.5%), ofloxacin (45.3%), amikacin (26.3%) and imipenem (16.8%), respectively. Seventy-six isolated strains were designated as multidrug resistant (MDR), while non-MDR was found in 19 strains (20.0%). Out of 76 MDR E. coli isolates, 41 (53.9%) were identified as positive for class II and 5 (6.5%) were positive for class III integron. Bioinformatics' analysis have shown that the sequences of our samples aligned along with many published sequences of integron II. Our findings further strengthen the significance of hospital-based and community E. coli strains on rising the burden of antimicrobial resistance.

Bibliometric Analysis of Machine Learning Applications in Ischemia Research.

OBJECTIVE: The objective of this study is to conduct a comprehensive bibliometric analysis to elucidate the landscape of machine learning applications in ischemia research. METHODS: The analysis can be divided in three sections: part 1 scrutinizes articles and reviews with "ischemia" in their titles, while part 2 further narrows the focus to publications containing both "ischemia" and "machine learning" in their titles. Additionally, part 3 delves into the examination of the top 50 most cited papers, exploring their thematic focus and co-word dynamics. RESULTS: The findings reveal a significant increase in publications over the years, with notable trends identified through detailed analysis. The growth in publication counts over time, the leading contributors, institutions, geographical distribution of research output and journals are numerically presented for part 1 and part 2. For the top 50 most cited papers the dynamics of co-words, which offer a nuanced understanding of thematic trends and emerging concepts, are presented. Based on the number of citations the top 10 authors were selected, and later for each, total number of publications, h-index, g-index and m-index are provided. Additionally, figures depicting the co-authorship network among authors, departments, and countries involved in the top 50 cited papers may enrich our comprehension of collaborative networks in ischemia research. CONCLUSION: This comprehensive bibliometric analysis provides valuable insights into the evolving landscape of machine learning applications in ischemia research.

Tuberculosis research advances and future trends: A bibliometric knowledge mapping approach.

The Gulf Cooperation Council (GCC) countries are more vulnerable to many transmissible diseases, including tuberculosis (TB). This study is to identify the scientific publications related to TB in the GCC countries using topic modeling and co-word analysis. A bibliometric analytic study. The R-package, VOSviewer software, IBM SPPS, and Scopus Analytics were used to analyze performance, hotspots, knowledge structure, thematic evolution, trend topics, and inter-gulf and international cooperation on TB in the past 30 years (1993-2022). A total of 1999 publications associated with research on GCC-TB were published. The annual growth rate of documents was 7.76%. Saudi Arabia is the most highly published, followed by the United Arab Emirates, Kuwait, Qatar, Oman, and Bahrain. The most-cited GC country is Kingdom Saudi Arabia, followed by Kuwait. One hundred sixty research institutions contributed to the dissemination of TB-related knowledge in the GCC, where the highest publishing organizations were King Saud University (Kingdom Saudi Arabia; n = 518). The number of publications related to TB is high in GCC Countries. The current tendencies indicated that GCC scholars are increasingly focused on deep learning, chest X-ray, molecular docking, comorbid covid-19, risk factors, and Mycobacterium bovis.

Cancer research in the United Arab Emirates from birth to present: A bibliometric analysis.

Background: Accumulating evidence indicates that the incidence of cancer is increasing in the United Arab Emirates (UAE). This analysis aimed to determine the current cancer research output in the UAE to guide future national research. Methods: The Scopus database was searched for cancer-related bibliographic data from the UAE. The number of publications, citation analysis, co-authorship of the author, institution, and country, keyword co-occurrence, and reference co-citations were analyzed using the R-studio bibliometrics package and VOSviewer software. Results: A total of 1678 journal articles were retrieved from 1981 to 2022. Cancer research in the UAE (UCR) is increasing at a rate of 14.64% (R-squared = 0.75; F = 46.477; P<0.001). The UAE had a 0.06% participation rate in terms of the number of original articles. The rate of international co-authorship is 40.23%. The U.S.A., U.K., Egypt, Saudi Arabia, India, and Canada had more than 100 co-authored documents from 156 countries that collaborated with the U.A.E. Conclusions: Compared to other nations, the UAE has fewer publications on cancer, although the number is growing. The current report provides an up-to-date and in-depth summary of the trends in UCR. This project is an excellent place for researchers interested in conducting data-mapping work in this field.

Gastroprotective effect of desmosdumotin C isolated from Mitrella kentii against ethanol-induced gastric mucosal hemorrhage in rats: possible involvement of glutathione, heat-shock protein-70, sulfhydryl compounds, nitric oxide, and anti-Helicobacter pylori activity.

BACKGROUND: Mitrella kentii (M. kentii) (Bl.) Miq, is a tree-climbing liana that belongs to the family Annonaceae. The plant is rich with isoquinoline alkaloids, terpenylated dihydrochalcones and benzoic acids and has been reported to possess anti-inflammatory activity. The purpose of this study is to assess the gastroprotective effects of desmosdumotin C (DES), a new isolated bioactive compound from M. kentii, on gastric ulcer models in rats. METHODS: DES was isolated from the bark of M. kentii. Experimental rats were orally pretreated with 5, 10 and 20 mg/kg of the isolated compound and were subsequently subjected to absolute ethanol-induced acute gastric ulcer. Gross evaluation, mucus content, gastric acidity and histological gastric lesions were assessed in vivo. The effects of DES on the anti-oxidant system, non-protein sulfhydryl (NP-SH) content, nitric oxide (NO)level, cyclooxygenase-2 (COX-2) enzyme activity, bcl-2-associated X (Bax) protein expression and Helicabacter pylori (H pylori) were also investigated. RESULTS: DES pre-treatment at the administered doses significantly attenuated ethanol-induced gastric ulcer; this was observed by decreased gastric ulcer area, reduced or absence of edema and leucocytes infiltration compared to the ulcer control group. It was found that DES maintained glutathione (GSH) level, decreased malondialdehyde (MDA) level, increased NP-SH content and NO level and inhibited COX-2 activity. The compound up regulated heat shock protein-70 (HSP-70) and down regulated Bax protein expression in the ulcerated tissue. DES showed interesting anti-H pylori effects. The efficacy of DES was accomplished safely without any signs of toxicity. CONCLUSIONS: The current study reveals that DES demonstrated gastroprotective effects which could be attributed to its antioxidant effect, activation of HSP-70 protein, intervention with COX-2 inflammatory pathway and potent anti H pylori effect.

Comprehensive analysis of research related to rehabilitation and COVID-19, hotspots, mapping, thematic evolution, trending topics, and future directions.

BACKGROUND: This study conducted a comprehensive analysis of research pertaining to the intersection of rehabilitation and COVID-19 (COV-REH). The main aim of this study is to analyze the thematic progression and hotspots, detect emerging topics, and suggest possible future research directions in the COV-REH. METHODS: Appropriate keywords were selected based on the Medical Subject Headings (MeSH) PubMed database and the Scopus database were used to retrieve a total of 3746 original studies conducted in the English language. The data extraction was performed on June 30, 2023. VOSviewer and Bibliometrix utilize CVS and BibTex files to facilitate the performance analysis and generate visual maps. The performance indicators reported for the research components of the COV-REH were compiled using the Scopus Analytics tool. RESULTS: From 2003 to 2023, 3470 authors from 160 organizations in 119 countries generated 3764 original research documents, with an annual growth of 53.73%. 1467 sources identified these scholarly works. Vitacca, M. (Italy), Harvard University (USA), and the USA published the most articles. This study included 54.1% of medical scholars. Telerehabilitation, exercise, quality of life, case reports, anxiety, and pulmonary rehabilitation were the primary themes of the COV-REH. One component of "telerehabilitation" is now the cardiac rehabilitation cluster. The trending topics in COV-REH are "symptoms," "protocol," and "community-based rehabilitation". CONCLUSIONS: This study proposed several significant research directions based on the current thematic map and its evolution. Given that COV-REH investigations have been determined to be multidisciplinary, this study contributes conceptually to several fields and has wide-ranging implications for practitioners and policymakers.

Diabetes mellitus research in Saudi Arabia: A bibliometric study (2010-2021).

Diabetes Mellitus (DM) causes global exhaustion, consumes economic resources, and has several risk factors. The bibliometric studies re-evaluate the research efforts on this illness using mathematical and statistical tools to indicate current research and future trends. This study examines KSA's DM research during 2010-2021. Data were acquired from Scopus and analyzed using VOSviewer and MS Excel. Several characteristics were examined to measure the quantity and quality of KSA-related DM articles. In total, 1,919 journal and conference papers were published. DM research included researchers from multidisciplinary sectors. Thirty-seven percent of them have ten or more scientific publications. Al-Daghri, N.M. (King Saud University) leads the pack. In total, 757 (39.44%) research projects got funding from 159 sources within and outside KSA. Memish, Z.A. is the most cited author. The Saudi Medical Journal has the most citations (1214). Al-Daghri, N.M. (KSU) collaborates the most. One hundred forty-one nations aided KSA's diabetes research. Egypt's High Institute of Public Health has the most scientific collaboration with KSA. Authors' and all Keywords analyses indicated a rich knowledge structure. Diabetes Care Journal has the most cocitations with 2,220 and a total link strength of 19,283, followed by The New England Journal of Medicine. The study results will be helpful to stakeholders to understand better the trends and performance of diabetes-related regional research, which will be beneficial.

Knowledge, attitudes, and practices (KAP) during the malaria elimination phase: A household-based cross-sectional survey.

Malaria is a major health problem in Southwestern Saudi Arabia. This study aimed to measure the level of community understanding of malaria transmission, protection, and treatment. A questionnaire-based cross-sectional study enrolled 1070 participants from 2 districts with different malaria prevalence rates in Jazan Province. The response rate was 97.27%. Of the 1070 total; 754 (70.5%) had heard about malaria. Sixty-seven percentage know that fever was the main symptom. Approximately 59.8% did not know that stagnant water is one of the most important locations for mosquito breeding. Nevertheless, we found that 50% of the participants knew that mosquitoes bite at night and 96.9% confirmed that mosquitoes did not bite during the day. The most effective sources of information were distributed leaflets (41.8%) and video awareness (31.9%). The most significant factors affecting participants knowledge were gender, residence, family members, income, and education (P < .05). Knowledge levels were satisfactory in this study, and the majority of participants exhibited adequate attitudes and practices related to malaria prevention. However, knowledge differences were observed with regard to the place of residence. Greater emphasis should be directed towards education programs in malaria-endemic areas to ensure complete eradication of malaria.

Erectogenic Effects of Clerodendron capitatum: Involvement of Phosphodiesterase Type-5 Inhibition.

Clerodendron capitatum (Willd) (family: verbenaceae) is locally named as Gung and used traditionally to treat erectile dysfunction. Therefore, the current study was designed to investigate the erectogenic properties of C. capitatum. The relaxation effect of this plant was tested on phenylephrine precontracted rabbit corpus cavernosum smooth muscle (CCSM). The effects of C. capitatum were also examined on isolated Guinea pig atria alone, in the presence of calcium chloride (Ca(2+) channel blocker), atropine (cholinergic blocker), and glibenclamide (ATP-sensitive K(+) channel blocker). These effects were confirmed on isolated rabbit aortic strips. The extract, when tested colorimetrically for its inhibitory activities on phosphordiesterase-5 (PDE-5) in vitro towards p-nitrophenyl phenyl phosphate (PNPPP), was observed to induce significant dose-dependent inhibition of PDE-5, with an ID(50) of 0.161 mg/ml (P < .05). In conclusion, our results suggest that C. capitatum possesses a relaxant effect on CCSM, which is attributable to the inhibition of PDE-5, but not mediated by the release calcium, activation of adrenergic or cholinergic receptors, or the activation of potassium channels.

Spectral Analysis and Antiulcer Potential of Lactuca sativa through the Amelioration of Proinflammatory Cytokines and Apoptosis Markers.

The objective of this study was to characterize the bioactive ingredients and antiulcer effects of Lactuca sativa leaves. Several bioactive chemicals were found in the cold methanolic extract of Lactuca sativa leaves after gas chromatography-mass spectrometry (GC-MS) research: 9,12-octadecadienoic acid (Z,Z)-, cyclononasiloxane, octadecamethyl-, n-hexadecanoic acid, Hexadecanoic acid, 2-hydroxy-1-(hydroxymethyl)ethyl, octadecanoic acid, 2-hydroxy-1-(hydroxymethyl)ethyl ester, 9-octadecenamide, (Z)-, hexadecanoic acid, stigmasterol, benzothiazole, ethyl iso-allocholate, and octacosane. Distinct fingerprint regions in GCMS indicated the existence of bioactive compounds. The leaf powder of Lactuca sativa (LPL) demonstrated substantial antiulcer properties at 400 mg/kg, which was almost equivalent to the standard drug at 20 mg/kg. The cytokine network was efficiently regulated by reducing the production of proinflammatory cytokines such as IL-1ß, IL-6, and TNF-α. The levels of caspase-3 and caspase-9 were also considerably lowered at p < 0.05 significant level.

Combination of zerumbone and cisplatin to treat cervical intraepithelial neoplasia in female BALB/c mice.

Recent in vitro and in vivo studies have demonstrated that zerumbone (ZER) possesses anticancer properties. The main objective of this study was to examine the effectiveness of the combination of ZER and cisplatin (CIS) to treat cervical intraepithelial neoplasia (CIN) in vivo. Microculture tetrazolium assay and immunohistochemistry of proliferating cellular nuclear antigen were used to study the antitumor effect of ZER. Prenatally exposed female BALB/c mice were used as a model. The progenies with CIN were injected peritoneally with isotonic sodium chloride solution (positive control), CIS, ZER, and a combination of both compounds. All treated and untreated mice were humanely killed, and serum and cervix were obtained for interleukin 6 analysis and histopathologic studies using hematoxylin and eosin staining, respectively. Zerumbone has revealed an antitumor effect on human cervical cancer cells and downregulates immunoexpression of proliferating cellular nuclear antigen (P < 0.05). In vivo study indicates that ZER at 16 mg/kg and CIS at 10 mg/kg have a regressing effect on CIN. The combination of ZER and CIS also showed similar effectiveness in regressing CIN. Our results indicate that the combination of ZER and CIS has modulated the serum level of interleukin 6 when compared with that in mice treated with isotonic sodium chloride solution (P < 0.05). The effectiveness of combining ZER and CIS could be further explored as a new therapeutic intervention of early precancerous stages of carcinogenesis before the invasive stage begins.

Evidence of the gastroprotective and anti- Helicobacter pylori activities of ß-mangostin isolated from Cratoxylum arborescens (vahl) blume.

PURPOSE: ß-Mangostin (BM) from Cratoxylum arborescens demonstrated various pharmacological activities such as anticancer and anti-inflammatory. In this study, we aimed to investigate its antiulcer activity against ethanol ulcer model in rats. MATERIALS AND METHODS: BM was isolated from C. arborescens. Gastric acid output, ulcer index, gross evaluation, mucus production, histological evaluation using hematoxylin and eosin and periodic acid-Schiff staining and immunohistochemical localization for heat shock protein 70 (HSP70) and Bax proteins were investigated. Possible involvement of reduced glutathione, lipid peroxidation, prostaglandin E2, antioxidant enzymes, superoxide dismutase and catalase enzymes, radical scavenging, nonprotein sulfhydryl compounds, and anti-Helicobacter pylori were investigated. RESULTS: BM showed antisecretory activity against the pylorus ligature model. The pretreatment with BM protect gastric mucosa from ethanol damaging effect as seen by the improved gross and histological appearance. BM significantly reduced the ulcer area formation, the submucosal edema, and the leukocytes infiltration compared to the ulcer control. The compound showed intense periodic acid-Schiff staining to the gastric mucus layer and marked amount of alcian blue binding to free gastric mucus. BM significantly increased the gastric homogenate content of prostaglandin E2 glutathione, superoxide dismutase, catalase, and nonprotein sulfhydryl compounds. The compound inhibited the lipid peroxidation revealed by the reduced gastric content of malondialdehyde. Moreover, BM upregulate HSP70 expression and downregulate Bax expression. Furthermore, the compound showed interesting anti-H. pylori activity. CONCLUSION: Thus, it could be concluded that BM possesses gastroprotective activity, which could be attributed to the antisecretory, mucus production, antioxidant, HSP70, antiapoptotic, and anti-H. pylori mechanisms.

Antisecretory, gastroprotective, antioxidant and anti-Helicobcter pylori activity of zerumbone from Zingiber zerumbet (L.) Smith.

BACKGROUND: Zingiber zerumbet Smith is a perennial herb, broadly distributed in many tropical areas. In Malaysia, it's locally known among the Malay people as "lempoyang" and its rhizomes, particularly, is widely used in traditional medicine for the treatment of peptic ulcer disease beyond other gastric disorders. AIM OF THE STUDY: The aim of the current study is to evaluate the gastroprotective effect of zerumbone, the main bioactive compound of Zingiber zerumbet rhizome, against ethanol-induced gastric ulcer model in rats. MATERIALS AND METHODS: Rats were pre-treated with zerumbone and subsequently exposed to acute gastric ulcer induced by absolute ethanol administration. Following treatment, gastric juice acidity, ulcer index, mucus content, histological analysis (HE and PAS), immunohistochemical localization for HSP-70, prostaglandin E2 synthesis (PGE2), non-protein sulfhydryl gastric content (NP-SH), reduced glutathione level (GSH), and malondialdehyde level (MDA) were evaluated in ethanol-induced ulcer in vivo. Ferric reducing antioxidant power assay (FRAP) and anti-H. pylori activity were investigated in vitro. RESULTS: The results showed that the intragastric administration of zerumbone protected the gastric mucosa from the aggressive effect of ethanol-induced gastric ulcer, coincided with reduced submucosal edema and leukocyte infiltration. This observed gastroprotective effect of zerumbone was accompanied with a significant (p <0.05) effect of the compound to restore the lowered NP-SH and GSH levels, and to reduce the elevated MDA level into the gastric homogenate. Moreover, the compound induced HSP-70 up-regulation into the gastric tissue. Furthermore, zerumbone significantly (p <0.05) enhanced mucus production, showed intense PAS stain and maintained PG content near to the normal level. The compound exhibited antisecretory activity and an interesting minimum inhibitory concentration (MIC) against H. pylori strain. CONCLUSION: The results of the present study revealed that zerumbone promotes ulcer protection, which might be attributed to the maintenance of mucus integrity, antioxidant activity, and HSP-70 induction. Zerumbone also exhibited antibacterial action against H. pylori.

Thymoquinone-loaded nanostructured lipid carriers: preparation, gastroprotection, in vitro toxicity, and pharmacokinetic properties after extravascular administration.

BACKGROUND: Nanostructured lipid carriers (NLCs), composed of solid and liquid lipids, and surfactants are potentially good colloidal drug carriers. Thymoquinone is the main bioactive compound of Nigella sativa. In this study, the preparation, gastroprotective effects, and pharmacokinetic (PK) properties of thymoquinone (TQ)-loaded NLCs (TQNLCs) were evaluated. METHOD: TQNLCs were prepared using hydrogenated palm oil (Softisan® 154), olive oil, and phosphatidylcholine for the lipid phase and sorbitol, polysorbate 80, thimerosal, and double distilled water for the liquid lipid material. A morphological assessment of TQNLCs was performed using various methods. Analysis of the ulcer index, hydrogen concentration, mucus content, and biochemical and histochemical studies confirmed that the loading of TQ into the NLCs significantly improved the gastroprotective activity of this natural compound against the formation of ethanol-induced ulcers. The safety of TQNLC was tested on WRL68 liver normal cells with cisplatin as a positive control. RESULTS: The average diameter of the TQNLCs was 75 ± 2.4 nm. The particles had negative zeta potential values of -31 ± 0.1 mV and a single melting peak of 55.85°C. Immunohistochemical methods revealed that TQNLCs inhibited the formation of ethanol-induced ulcers through the modulation of heat shock protein-70 (Hsp70). Acute hepatotoxic effects of the TQNLCs were not observed in rats or normal human liver cells (WRL-68). After validation, PK studies in rabbits showed that the PK properties of TQ were improved and indicated that the drug behaves linearly. The Tmax, Cmax, and elimination half-life of TQ were found to be 3.96 ± 0.19 hours, 4811.33 ± 55.52 ng/mL, and 4.4933 ± 0.015 hours, respectively, indicating that TQ is suitable for extravascular administration. CONCLUSION: NLCs could be a promising vehicle for the oral delivery of TQ and improve its gastroprotective properties.

Gastroprotective mechanism of Bauhinia thonningii Schum.

ETHNOPHARMACOLOGICAL RELEVANCE: Bauhinia thonningii Schum. (Cesalpiniaceae) is locally known as Tambarib and used to treat various diseases including gastric ulcer. AIM OF THE STUDY: The current study aims to evaluate the gastroprotecive mechanism(s) of methanolic (MEBT) and chloroform (CEBT) extracts of Bauhinia thonningii leaves on ethanol-induced gastric ulceration. MATERIALS AND METHODS: Gastric acidity, quantification and histochemistry of mucus, gross and microscopic examination, nitric oxide, lipid peroxidation, 2D gel electrophoresis, mass spectroscopy and biochemical tests were utilized to assess the mechanism(s) underlying the gastroprotective effects of MEBT and CEBT. Effect of these extracts into lipopolysaccharide/interferon-γ stimulated rodent cells were done in vitro. In vitro and in vivo toxicity studies were also conducted. Antioxidant activities of MEBT and CEBT were examined using DPPH, FRAP and ORAC assays. Phytochemical analyses of MEBT and CEBT were conducted using chemical and spectroscopic methods. RESULTS: Gross and histological features confirmed the anti-ulcerogenic properties of Bauhinia thonningii. Gastroprotective mechanism of MEBT was observed to be mediated through the modulation of PAS-reactive substances, MDA and proteomics biomarkers (creatine kinase, malate dehydrogenase, ATP synthase, actin and thioredoxin). MEBT and CEBT showed no significant in vitro and in vivo effects on nitric oxide. Methanolic extract (MEBT) showed superior gastroprotective effects, polyphenolic content and antioxidant activities compared to CEBT. The plant extracts showed no in vitro or in vivo toxicity. CONCLUSION: It could be concluded that MEBT possesses anti-ulcer activity, which could be attributed to the inhibition of ethanol-induced oxidative damage and the intervention in proteomic pathways but not the nitric oxide pathway.

Dentatin isolated from Clausena excavata induces apoptosis in MCF-7 cells through the intrinsic pathway with involvement of NF-κB signalling and G0/G1 cell cycle arrest: a bioassay-guided approach.

ETHNOPHARMACOLOGICAL RELEVANCE: Clausena excavata Burm. f. has been used in folk medicines in eastern Thailand for the treatment of cancer. MATERIALS AND METHODS: To investigate the apoptosis mechanism, we isolated dentatin (DTN) from this plant using a bioassay-guided approach. DTN-induced cytotoxicity was observed with the MTT assay. Acridine orange/propidium iodide staining was used to detect cells in early apoptosis and high content screening (HCS) to observe nuclear condensation, cell permeability, mitochondrial membrane potential (MMP) and cytochrome c release. Apoptosis was confirmed with a clonogenic assay, DNA laddering and caspase 3/7 and 9 assays. Reactive oxygen species (ROS) formation, Bcl-2 and Bax expression, and cell cycle arrest were also investigated. The involvement of nuclear factor-kappa B (NF-κB) was analysed with the HCS assay. RESULTS: A significant increase in chromatin condensation in the cell nucleus was observed by fluorescence analysis. Apoptosis was confirmed by the reduced number of colonies in the clonogenic assay and the increased number of cellular DNA breaks in treated cells observed as a DNA ladder. Treatment of MCF-7 cells with DTN encouraged apoptosis with cell death-transducing signals that reduced MMP by down-regulation of Bcl-2 and up-regulation of Bax, triggering cytochrome c release from the mitochondria to the cytosol. The released cytochrome c triggered the activation of caspase 9 followed by the executioner caspase 3/7. DTN treatment significantly arrested MCF-7 cells at the G0/G1 phase (p<0.05) and ROS was significantly elevated. Moreover, DTN significantly blocked the induced translocation of NF-κB from cytoplasm to nucleus. CONCLUSION: Together, the results demonstrated that the DTN isolated from Clausena excavata inhibited the proliferation of MCF-7 cells, leading to cell cycle arrest and programmed cell death, which was confirmed to occur through the mitochondrial pathway with involvement of the NF-κB signalling pathway.

Pyranocycloartobiloxanthone A, a novel gastroprotective compound from Artocarpus obtusus Jarret, against ethanol-induced acute gastric ulcer in vivo.

Pyranocycloartobiloxanthone A (PA), a xanthone derived from the Artocarpus obtusus Jarret, belongs to the Moraceae family which is native to the tropical forest of Malaysia. In this study, the efficacy of PA as a gastroprotective compound was examined against ethanol-induced ulcer model in rats. The rats were pretreated with PA and subsequently exposed to acute gastric lesions induced by absolute ethanol. The ulcer index, gastric juice acidity, mucus content, histological analysis, glutathione (GSH) levels, malondialdehyde level (MDA), nitric oxide (NO) and non-protein sulfhydryl group (NP-SH) contents were evaluated in vivo. The activities of PA as anti-Helicobacter pylori, cyclooxygenase-2 (COX-2) inhibitor and free radical scavenger were also investigated in vitro. The results showed that the oral administration of PA protects gastric mucosa from ethanol-induced gastric lesions. PA pretreatment significantly (p<0.05) restored the depleted GSH, NP-SH and NO levels in the gastric homogenate. Moreover, PA significantly (p<0.05) reduced the elevated MDA level due to ethanol administration. The gastroprotective effect of PA was associated with an over expression of HSP70 and suppression of Bax proteins in the ulcerated tissue. In addition, PA exhibited a potent FRAP value and significant COX-2 inhibition. It also showed a significant minimum inhibitory concentration (MIC) against H. pylori bacterium. The efficacy of PA was accomplished safely without the presence of any toxicological parameters. The results of the present study indicate that the gastroprotective effect of PA might contribute to the antioxidant and anti-inflammatory properties as well as the anti-apoptotic mechanism and antibacterial action against Helicobacter pylori.