Hepatoprotective effects of linalool against liver ischemia-reperfusion: the role of Nrf2/HO-1/NQO1 and TLR4/RAGE/NFκB pathways.

OBJECTIVE: Hepatic ischemia-reperfusion (H I/R) injury arises due to a temporary obstruction followed by the re-establishment of blood supply to the liver. Linalool (LIN), a main volatile constituent of essential oils in numerous aromatic plant species, exhibited various medicinal and pharmacological actions. This study investigated the protective effect of LIN on the status of H I/R, with the study of the possible mechanisms. In addition, linalool's antagonistic effects were tested against several metabolic targets using in silico molecular docking technique. MATERIALS AND METHODS: Wistar rats were allocated into five groups. Sham and LIN + Sham groups in which animals were administered either vehicle (1% CMC) or LIN (200 mg/kg/day) orally for two weeks. H I/R group in which rats were administered 1% CMC for two weeks and then experienced hepatic ischemia for 60 min followed by 6 hours of reperfusion. LIN 100 + H I/R and LIN 200 + H I/R groups in which rats were pretreated with LIN (100, 200 mg/kg/day) respectively for two weeks, then subjected to H I/R. RESULTS: H I/R-induced injury resulted in impaired liver function and activated Keap1/Nrf2/HO-1/NQO1 and HMGB1/TLR4/RAGE/NFкB pathways with subsequent oxidative stress, inflammation, and apoptosis. LIN pretreatment alleviated I/R-induced impairment in liver function, promoted Keap1/Nrf2/HO-1/NQO1, and mitigated the HMGB1/TLR4/RAGE/NFкB pathway. LIN pre-administration deterred adhesion molecule, neutrophils infiltration, RAGE, IL-1ß, IL-6, TNF-α, and apoptosis. CONCLUSIONS: LIN demonstrated hepato-protective effects against H I/R via instigation Keap1/Nrf2/HO-1/NQO1 and mitigating the HMGB1/TLR4/RAGE/NFкB pathways with subsequent deterring oxidative stress, inflammation, and apoptosis.

Studying the actions of sage and thymoquinone combination on metabolic syndrome induced by high-fat diet in rats.

OBJECTIVE: High-fat diet is one of the most imperative risk factors for cardiovascular disorders. Thymoquinone (TQ) is one of the active pharmacological components of Nigella sativa (black cumin). Salvia officinalis L. (sage) has been demonstrated to have diverse pharmacological actions. The main objective of this study was to determine the effects of sage and TQ combination on hyperglycemia, oxidative stress, blood pressure, and lipid profile in rats fed with a high-fat diet (HFD). MATERIALS AND METHODS: Wistar male rats were divided into five groups; normal diet (ND) and HFD, in which rats were fed with a normal diet or HFD for 10 weeks, respectively. In HFD + sage group, animals were administered sage essential oil (0.052 ml/kg) orally along with HFD. In HFD + TQ group, rats were administered TQ (50 mg/kg) orally with HFD. In HF + sage + TQ group, animals received sage + TQ along with HFD. Blood glucose (BGL) and Fast serum insulin (FSI) levels, oral glucose tolerance test, blood pressure, liver function tests, plasma, and hepatic oxidative stress markers, antioxidant enzymes, and glutathione content, and lipid profile were measured. RESULTS: Sage and TQ combination decreased the final body weight, weight gain, BGL, FSI, and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR). The combination also lowered systolic and diastolic arterial pressures and liver function enzymes. The combination deterred lipid peroxidation, advanced protein oxidation product, and nitric oxide amplification, as well as restoring the superoxide dismutase, catalase activities, and glutathione content in plasma and hepatic tissue. Sage and TQ combination reduced the plasma total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) levels and amplified high-density lipoprotein (HDL). CONCLUSIONS: The results of the current study verified that sage essential oil, together with TQ exhibited hypoglycemic, hypolipidemic, and antioxidant actions and thus could be a valuable addition to diabetes management.

ß-caryophyllene ameliorates hepatic ischemia reperfusion-induced injury: the involvement of Keap1/Nrf2/HO 1/NQO 1 and TLR4/NF-κB/NLRP3 signaling pathways.

OBJECTIVE: Hepatic ischemia-reperfusion (H I/R) injury is a frequent clinical event during which the leading contributing players are inflammation and oxidative stress responses. ß-caryophyllene (BCP), a natural bicyclic sesquiterpene, is an essential oil component of different plant species and edibles. This study aims to identify whether BCP pretreatment could avert H I/R injury with inspections of the underlying mechanisms. MATERIALS AND METHODS: Animals were devised into five groups; Sham and BCP + Sham; the animals were administered saline or BCP (200 mg/kg, orally) respectively; H I/R group, the animals were administered saline orally for 14 days before induction of H I/R; BCP100 and BCP200, the animals were administered BCP (100 and 200 mg/kg, respectively) for 14 days, followed by induction of H I/R. RESULTS: H I/R showed markedly increased ALT, AST, MDA, and lowered antioxidant enzyme activities, while the Nrf2/HO1/NQO1 pathway components were significantly augmented. The TLR4/NF-κB/NLRP3 elements were deterred, and subsequently, escalations in the inflammatory mediators (IL-1ß, IL-6, and TNF-α), adhesion molecule ICAM-1, neutrophils infiltration (MPO), and apoptotic markers were observed. Pretreatment with BCP amplified the antioxidant enzyme activities and Keap1/Nrf2/HO1/NQO1 pathway components. BCP pretreatment lowered TLR4/NF-κB/NLRP3 pathway elements, which mitigated inflammatory mediators, ICAM-1, MPO, and apoptotic markers. CONCLUSIONS: The protective effect of BCP against hepatic I/R induced injury might be accomplished via mitigation of oxidative stress by regulating the Keap1/Nrf2/HO1/NQO1 pathway and inhibition of the inflammatory process via manipulating the TLR4/ NF-κB/ NLRP3, reflected by inflammatory markers, neutrophils recruitment, and adhesion molecules reduction. BCP might be a potential therapeutic agent for alleviating hepatic I/R-induced injury.

Potential genetic biomarker of Saudi Arabian patients with colorectal cancer.

Colorectal cancer (CRC) is one of the leading causes of cancer deaths globally. We implemented a comprehensive literature review regarding CRC genetics studies to offer a perception into the genes associated with CRC recognized in Saudi patients. Definite genetic variants in ABCB1, ADIPOQ, CTNNB1, SFRP3, LRP6, CYP19A1, PARP-1, TDG genes exhibited significant protection against CRC development in Saudi population. Whereas, other gene mutations in ABCB1, ABCC1, CASR, IL-17F, NOTCH1, NOTCH4, PRNCR1, TDG, TLR2, TLR4, TLR-9, TSLP, TSLPR and TNF-α genes showed irrelevant correlation with CRC risk in Saudi Arabia. On the other hand, specific mutations in ABCC1, ADIPOQ, CYP1A1, KIR, IL-17A, MMP2, NOTCH3, PRNCR1, RETN, TDG, TLR2, BRAF, PARP-1, TLR4, TLR-9, TNF-α, TSLP and XRCC1 genes demonstrated a substantial augmented CRC risk development in Saudi patients. Furthermore, ATR, ATM, BMI1, CCAT1, Chk1, Chk2, COX-2, FoxM1, FSCN1, Ki67, MALAT1, miR-29, miR-34a, miR-92, miR-182-5, PANDAR, PIK3CA, TIGAR over-expression revealed a robust association with CRC in Saudi Arabia (KSA). Moreover, gene alterations in APC, EGFR, FBXW7, TP53, PTEN, K-ras genes were concomitant in CRC. As well as, lower expression of MLH1, MSH2, MSH6, PMS2, EPCAM and MUTYH genes were recognized in LS patients and future CRC Saudi patients. These gene mutations may be used as diagnostic and/or prognostic genetic markers in CRC Saudi patients and could offer a potential therapeutic target for CRC management.

Identification of epilepsy concomitant candidate genes recognized in Saudi epileptic patients.

Saudi Genome program is a revolutionary nationwide transformation initiative of Saudi Vision 2030. The program goals are to recognize and reduce the incidence of genetic diseases in the Kingdom of Saudi Arabia (KSA). Accordingly, the program will establish the foundation for personalized and genomic medicine in the KSA. Epilepsy has a high prevalence in KSA reaching around 6.54 of 1000 individuals with a subsequent massive financial burden. One of the main risk factors for this high prevalence and associated with increased risk of epilepsy development is consanguinity marriage, which is traditional in KSA. In this review, we executed a comprehensive state-of-art literature review regarding epilepsy genetics to offer a perception into the genes associated with epilepsy recognized in Saudi epileptic patients. Several genes' mutations were incorporated in this review including AFG3L2, ASPM, ATN1, ATP1A2, BMP5, CCDC88A, C12orf57, DNAJA1, EML1, ERLIN2, FRRS1L, GABRG3, NRXN3, MDH1, KCNJ10, KCNMA1, KCNT1, KIAA0226, OPHN1, PCCA, PCCB, PEX, PGAP2, PI4K2A, PODXL, PRICKLE1, PNKP, RELN, SCN2A, SCN1B, SLC2A1, SLC19A3, SLC25, SIAH1, SYNJ1, SZT2, TBCK, TMX2, TSC1, TSC2, TSEN, WDR45B, WWOX, UBR, UGDH, and YIF1B. For each of these genes, we tried to explain a little about the gene associated proteins and their roles in epilepsy development.

Silver nanoparticles green synthesis via cyanobacterium Phormidium sp.: characterization, wound healing, antioxidant, antibacterial, and anti-inflammatory activities.

OBJECTIVE: Green synthesis of silver nanoparticles (AgNPs) using cyanobacterial platforms is becoming more popular nowadays. In this study, the filamentous non-heterocystous cyanobacterium Phormidium sp. was used for AgNPs production. Then, it was investigated for its antibacterial and wound-healing properties. MATERIALS AND METHODS: The cyanobacterium cultures were challenged by AgNO3, and the obtained nanoparticles were characterized using UV and FTIR spectrometric methods. The antimicrobial activity of AgNPs was scrutinized against MRSA either alone or in combination 0.5% chloramphenicol. The green synthesized AgNPs were tested for their skin wound healing activity using several wound models at different concentrations. RESULTS: The cyanobacterial culture extract showed the characteristic surface plasmon resonance peak at 440 nm for AgNPs. Different functional groups that could contribute to the reduction of Ag+ to AgNPs or the stabilization of the nanoparticles were identified by the FTIR. AgNPs potentiated the antimicrobial activity of chloramphenicol against MRSA. Green synthesized silver nanoparticles have demonstrated topical effectiveness in different wound models, including excision, incision, and burn. Significant wound improvement and the increase in wound closure rate, hydroxyproline content, and the reduction in epithelialization period confirmed the wound healing potency of AgNPs. The enzymatic antioxidant level escalation and inflammatory cytokines attenuation supported the AgNPs substantial effect on wound repairing. CONCLUSIONS: Biogenic AgNPs produced by Phormidium sp. showed significant antimicrobial together with wound healing abilities.

Protective mechanisms of piperine against acetaminophen-induced hepatotoxicity may be mediated through TGFBRAP1.

OBJECTIVE: To investigate the possible protective mechanisms of piperine against acetaminophen (APAP)-induced hepatotoxicity in mice. MATERIALS AND METHODS: Mice were given APAP (650 mg/kg i.p. once) with or without pretreatment with piperine (50 mg/kg/day orally for 3 days). RESULTS: APAP caused liver toxicity as indicated by increased serum alanine aminotransferase and liver microscopic pathology, decreased hepatic superoxide dismutase and glutathione reductase activities, without affecting nuclear factor erythroid 2-related factor 2 (Nrf2) expression. APAP administration induced inflammation and apoptosis manifested as increased NF-κB p65 and dysregulation of caspase 3/Bcl2 expression, respectively. In addition, APAP increased the expression of transforming growth factor-ß receptor-associated binding protein 1 (TGFBRAP1). On the other hand, pretreatment with piperine improved liver function and structure, reserved hepatic antioxidative defense, and attenuated inflammatory and apoptotic markers. Interestingly, piperine administration enhanced hepatic TGFBRAP1 expression compared to APAP alone. CONCLUSIONS: The hepatoprotective effects of piperine against APAP are mediated via its antioxidant, anti-inflammatory, and anti-apoptotic effects, in addition to regulation of TGFBRAP1.