Inhibition of both NOX and TNF-α exerts substantial renoprotective effects in renal ischemia reperfusion injury rat model.

BACKGROUND AND AIMS: Acute kidney injury (AKI) due to renal ischemia-reperfusion injury (RIRI) is associated with high morbidity and mortality, with no renoprotective drug available. Previous research focused on single drug targets, yet this approach has not reached translational success. Given the complexity of this condition, we aimed to identify a disease module and apply a multitarget network pharmacology approach. METHODS: Identification of a disease module with potential drug targets was performed utilizing Disease Module Detection algorithm using NADPH oxidases (NOXs) as seeds. We then assessed the protective effect of a multitarget network pharmacology targeting the identified module in a rat model of RIRI. Rats were divided into five groups; sham, RIRI, and RIRI treated with setanaxib (NOX inhibitor, 10 mg/kg), etanercept (TNF-α inhibitor, 10 mg/kg), and setanaxib and etanercept (5 mg/kg each). Kidney functions, histopathological changes and oxidative stress markers (MDA and reduced GSH) were assessed. Immunohistochemistry of inflammatory (TNF-α, NF-κB) apoptotic (cCasp-3, Bax/Bcl 2), fibrotic (α-SMA) and proteolysis (MMP-9) markers was performed. RESULTS: Our in-silico analysis yielded a disease module with TNF receptor 1 (TNFR1A) as the closest target to both NOX1 and NOX2. Targeting this module by a low-dose combination of setanaxib, and etanercept, resulted in a synergistic effect and ameliorated ischemic AKI in rats. This was evidenced by improved kidney function and reduced expression of inflammatory, apoptotic, proteolytic and fibrotic markers. CONCLUSIONS: Our findings show that applying a multitarget network pharmacology approach allows synergistic renoprotective effect in ischemic AKI and might pave the way towards translational success.

Adrenergic receptors blockade alleviates dexamethasone-induced neurotoxicity in adult male Wistar rats: Distinct effects on ß-arrestin2 expression and molecular markers of neural injury.

BACKGROUND: Dexamethasone-induced neurotoxicity has been previously reported. However, the molecular mechanisms are still not completely understood. OBJECTIVES: The current work aimed to investigate the modulatory effects of α- and ß-adrenergic receptors on dexamethasone-induced neurotoxicity in rats focused on changes in ß-arrestin2 and molecular markers of neural injury in cerebral cortex. METHODS: Male Wistar rats were subcutaneously injected with dexamethasone (10 mg/kg/day) for 7 days to induce neural injury in the cerebral cortex. The experiment involved 5 groups: control, dexamethasone, carvedilol, propranolol, and doxazosin. In the last 3 groups, drugs were given 2 hours before dexamethasone injection. At the end of experiment, brain samples were collected for measurement of brain derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), kinase activity of protein kinase B (Akt), diacylglycerol (DAG), α-smooth muscle actin (α-SMA), Smad3, ß-amyloid and phospho-tau protein levels in addition to histopathological examination of brain tissue using hematoxylin-eosin, Nissl, and Sirius red stains. Moreover, ß-arrestin2 levels in the cerebral cortex were measured using immunohistochemical examination. RESULTS: Dexamethasone slightly reduced brain weight and significantly decreased BDNF, Akt kinase activity and ß-arrestin2 but markedly induced degeneration of cortical neurons and significantly increased GFAP, DAG, α-SMA, Smad3, ß-amyloid and phospho-tau protein levels compared to controls. Carvedilol, propranolol, and doxazosin reversed all dexamethasone-induced molecular changes and slightly ameliorated the histopathological changes. Carvedilol significantly increased brain weight and ß-arrestin2 levels compared to dexamethasone, propranolol, and doxazosin groups. CONCLUSION: blocking α- and/or ß-adrenergic receptors alleviate dexamethasone-induced neurotoxicity despite their distinct effects on ß-arrestin2 levels in the cerebral cortex.

Dermato-cosmeceutical properties of Pseudobombax ellipticum (Kunth) Dugand: Chemical profiling, in vitro and in silico studies.

Plant extracts and their individual components have been used to manage skin aging for several decades. Recently, the discovery of new natural bioactive agents, that not only enhance the skin health but also offer protection against various deleterious factors, such as free radicals, ultraviolet radiation, and microbial infections, has been a potential target by many researchers. The aim of the current work was to investigate the phytochemical profile of an ethanol bark extract from Pseudobombax ellipticum, and to evaluate its antioxidant, antiaging and antibacterial activities in vitro. Molecular docking and molecular dynamics studies were adopted to estimate and confirm the binding affinity of several compounds and explain their binding pattern at the binding sites of four target enzymes associated with skin aging, namely collagenase, elastase, tyrosinase, and hyaluronidase. HPLC-MS/MS analysis led to the tentative identification of 35 compounds comprising phenolic acids, and their glycosides, procyanidins and flavonoid glycosides. The extract demonstrated a promising in vitro antioxidant activity in the DPPH and FRAP assays (IC50 56.45 and 15.34 µg/mL, respectively), and was able to inhibit the aforementioned key enzymes with comparable results to the reference drugs. In addition, the extract (6.25 mg/mL) inhibited the biofilm production of Pseudomonas aeruginosa and diminished the swimming and swarming motilities. The docked compounds revealed appreciable binding energy with the tested enzymes and were stable throughout the molecular dynamic simulations. In view of this data, P. ellipticum bark can be regarded as a good candidate for prospective application in derma-cosmeceutical preparations.

Leonotis ocymifolia (Burm.f.) Iwarsson aerial parts aqueous extract mitigates cisplatin-induced nephrotoxicity via attenuation of inflammation, and DNA damage.

Herein, we explored the protective effect of Leonotis ocymifolia (Burm.f.) Iwarsson aerial parts extract (LO) against cisplatin (CP)-induced nephrotoxicity in rats and profiled their phytocontents. A total of 31 compounds belonging to organic and phenolic acids and their glycosides as well as flavonoids and their O- and C-glycosides were identified through LC-MS/MS. The DPPH and FRAP assays revealed that the extract had powerful antioxidant properties. The in vivo results demonstrated that administering LO extract for 30 days (40 and 80 mg/kg b. w.) significantly improved the altered renal injury markers via reducing creatinine (high dose only) and uric acid levels compared to the Cp-group. The deleterious action of cisplatin on renal oxidative stress markers (GSH, MDA, SOD, and CAT) were also mitigated by LO-pretreatment. The reduction of the inflammatory marker (IL-6), and inhibition of DNA fragmentation, highlighted the prophylactic action of LO in kidney tissue. Molecular docking followed by a 100 ns molecular dynamic simulation analyses revealed that, amongst the 31 identified compounds in LO, chlorogenic and caffeoylmalic acids had the most stable binding to IL-6. The nephroprotective effects were further confirmed by histopathological observations, which showed improvement in ultrastructural changes induced by cisplatin. The observed findings reinforce the conclusion that L. ocymifolia extract exerts nephroprotective properties, which could be related to its antioxidant and anti-inflammatory activities. Further studies are required to determine the therapeutic doses and the proper administration time.

Thymus satureioides Coss. combats oral ulcer via inhibition of inflammation, proteolysis, and apoptosis.

Oral ulcer is a frequent condition that commonly affects the tongue and in which 75% of the patients experience pain, and 25% report taste changes. The available therapies are not sufficiently effective for rapid and complete healing of tongue ulcers. We previously annotated the metabolites of Thymus satureioides (TS) aerial parts and reported their antioxidant, dermacosmeceutical and hepatoprotective properties. In this study, we performed in silico analysis, by applying network pharmacology and molecular docking, followed by experimental validation of the effect of local application of T. satureioides (TS) gel at two different concentrations on the healing of acetic-acid-induced tongue ulcer in rats. Salvianolic acid A, phloretic acid caffeate, rosmarinic acid, apigenin, and luteolin were the top bioactive ingredients of TS extract. Network pharmacology showed that the most relevant targets of these active constituents were TLR4, COX-2, MMP-9, TNF-α, and Caspase-3. Molecular docking showed that rosmarinic acid and salvianolic acid had a relatively strong binding affinity, compared to the other compounds, toward all the target proteins. Experimental validation in tongue ulcer model in rats and immunohistochemistry experiments showed that application of a gel containing TS extract (5 and 10%) was effective in healing the tongue ulcer via downregulation of COX-2, TNF-α, MMP-9, and Caspase-3. This study suggests that T. satureioides extract could act as a topical treatment for tongue ulcers by combating inflammation, apoptosis, and proteolysis. The possible treatment potential of some constituents including rosmarinic acid and salvianolic acid in oral ulcerations awaits further investigations to confirm their potency.

Thymus satureioides Coss.: Mineral Composition, Nutritional Value, Phytochemical Profiling, and Dermatological Properties.

Zaitra, Thymus satureioides, is an aromatic plant with a long history of use in traditional medicine. In this study, we assessed the mineral composition, nutritional value, phytocontents, and dermatological properties of the aerial parts of T. satureioides. The plant contained high contents of calcium and iron, moderate levels of magnesium, manganese, and zinc, and low contents of total nitrogen, total phosphorus, total potassium, and copper. It is rich in several amino acids, including asparagine, 4-hydroxyproline, isoleucine, and leucine, and the essential amino acids account for 60.8%. The extract contains considerable amounts of polyphenols and flavonoids (TPC = 118.17 mg GAE/g extract and TFC = 32.32 mg quercetin/g extract). It also comprises 46 secondary metabolites, identified through LC-MS/MS analysis, belonging to phenolic acids, chalcones, and flavonoids. The extract elicited pronounced antioxidant activities, inhibited the growth of P. aeruginosa (MIC = 50 mg/mL), and reduced biofilm formation by up to 35.13% using the » sub-MIC of 12.5 mg/mL. Moreover, bacterial extracellular proteins and exopolysaccharides were diminished by 46.15% and 69.04%, respectively. Likewise, the swimming of the bacterium was impaired (56.94% decrease) in the presence of the extract. In silico, skin permeability and sensitization effects revealed that out of the 46 identified compounds, 33 were predicted to be exempt from any skin sensitivity risk (Human Sensitizer Score ≤ 0.5), while extensive skin permeabilities were observed (Log Kp = -3.35--11.98 cm/s). This study provides scientific evidence about the pronounced activities of T. satureioides, supports its traditional uses, and promotes its utilization in the development of new drugs, food supplements, and dermatological agents.

Salix babylonica L. mitigates pancreatic damage by regulating the Beclin-P62/SQSTM1 autophagy pathway in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Salix babylonica L. belongs to the genus Salix, family Salicaceae. It is traditionally used as an antipyretic, antirheumatic, antidiabetic and for the treatment of ulcers and parasite skin diseases. It also has a range of pharmacological effects, such as anti-inflammatory, anti-tumor, antioxidant, and antibacterial effects. However, there are no reports on the phytochemical profile and efficacy of its leaves extract to modulate dexamethasone induced pancreatic damage. AIM OF THE STUDY: The present study was performed to annotate the phytoconstituents of Salix babylonica leaf extract and explore whether and how it could modulate dexamethasone-induced pancreatic damage and the role of oxidative stress and autophagy in mediating its protective effects. MATERIALS AND METHODS: Wistar rats were used for this study. Salix babylonica in two dose levels (100 and 200 mg/kg) or metformin (50 mg/kg) was given by oral gavage concurrently with dexamethasone which was injected SC in a dose of 10 mg/kg for 4 consecutive days. RESULTS: LC-MS analysis furnished 84 secondary metabolites belonging to phenolic acids, salicinoids, proanthocyanidins, flavonoids, cyclohexanediol glycosides, and hydroxy fatty acids. S. babylonica at both dose levels and metformin decreased the elevated pancreatic beclin while elevated the decreased pancreatic P62/SQSTM1 content compared to dexamethasone. These effects were associated with improved histopathological changes, glycemic and lipid parameters indicating that there might be a connection between autophagy and dexamethasone-induced pancreatic damage. Given that the level of GSH was negatively correlated with the levels of beclin and positively correlated with P62/SQSTM1, while both MDA and NO levels were positively correlated with beclin and negatively correlated with P62/SQSTM1, it seems that dexamethasone induced autophagy may be attributed to dexamethasone induced pancreatic oxidative stress. CONCLUSION: Our results indicate that S. babylonica protects pancreatic tissues against dexamethasone-induced damage by decreasing oxidative stress and its associated autophagy. Our study reveals a new mechanism for dexamethasone effects on pancreas and shows the potential therapeutic role of S. babylonica in mitigating dexamethasone adverse effects on pancreas and establishes the groundwork for future clinical applications.

Cupressus arizonica Greene: Phytochemical Profile and Cosmeceutical and Dermatological Properties of Its Leaf Extracts.

For many decades, natural resources have traditionally been employed in skin care. Here, we explored the phytochemical profile of the aqueous and ethanolic leaf extracts of Cupressus arizonica Greene and assessed their antioxidant, antiaging and antibacterial activities in vitro. Liquid chromatography-mass spectrometry (LC-MS/MS) analysis led to the tentative identification of 67 compounds consisting mainly of phenolic and fatty acids, diterpene acids, proanthocyanidins and flavonoid and biflavonoid glycosides. The aqueous extract demonstrated substantial in vitro antioxidant potential at FRAP and DPPH assays and inhibited the four target enzymes (collagenase, elastase, tyrosinase, and hyaluronidase) engaged in skin remodeling and aging with IC50 values close to those of the standard drugs. Moreover, the aqueous extract at 25 mg/mL suppressed biofilm formation by Pseudomonas aeruginosa, a bacterial pathogen causing common skin manifestations, and decreased its swarming and swimming motilities. In conclusion, C. arizonica leaves can be considered a promising candidate for potential application in skin aging.

Apple (Malus domestica Borkh) leaves attenuate indomethacin-induced gastric ulcer in rats.

Malus domestica Borkh, the apple tree, exhibited numerous pharmacological properties including antioxidant, neuroprotective, anti-inflammatory, anticancer and antimicrobial activities. The present work aimed to annotate the secondary metabolites from a butanol fraction of apple leaves (BLE), evaluate the gastro-protective and healing effects of this fraction against indomethacin-induced gastric ulcers in rats and to identify its mechanism of action. BLE (100, and 200 mg/kg) was orally administered in rats as an acute treatment against indomethacin-induced gastric ulcer in comparison with famotidine as reference anti-ulcer drug. The stomachs of rats were collected to determine the ulcer index, the preventive ratio, measure the activity of glutathione peroxidase (GPx), and estimate the expression of cyclooxygenase-2 (COX-2), and heat shock protein 70 (HSP70). Furthermore, we evaluated both inflammatory and oxidative stress markers in the gastric tissues. We also performed histopathological study of gastric mucosa using H&E stain and periodic Schiff base stain to evaluate both gastric injury scores and gastric mucus content respectively. Pretreatment with BLE markedly lowered the severity of gastric injury induced by indomethacin, decreased oxidative stress, inflammatory cytokines, and COX-2 expression in the examined gastric tissues. The gastric healing effect of BLE was associated with increased mucoglycoproteins, and HSP70 expression. Additionally, gastric healing effect of high dose of BLE was superior to that of famotidine in decreasing gastric injury scores, COX-2, inflammatory cytokines, lipid peroxidation and in increasing gastric mucin content, HSP70, and reduced glutathione. These findings indicate that BLE is effective in accelerating ulcer healing by boosting HSP70 expression, and decreasing COX-2 expression, oxidative stress, and gastric inflammation which might be related to the presence of 21 phytoconstituents.

Moxonidine ameliorates cardiac injury in rats with metabolic syndrome by regulating autophagy.

AIMS: Reduced cardiac autophagy, ischemic injury, sympathetic overactivity, and apoptosis all contribute to metabolic syndrome (MetS)-associated cardiovascular risks. NR4A2, an orphan nuclear receptor NR4A family member, induces autophagy while suppressing apoptosis in myocardial infarction. Moxonidine, a sympathoinhibitor imidazoline1 receptor (I1R) agonist, has beneficial metabolic and hemodynamic effects; however, whether autophagy and/or NR4A2 signaling are involved in moxonidine's cardiovascular effects via I1R activation, is unknown, and is the aim of this study. MATERIALS AND METHODS: To induce MetS, rats were fed 3 % salt in their diet and 10 % fructose in their drinking water for 12 weeks. MetS-rats were given either moxonidine (6 mg/kg/day, gavage), efaroxan (I1R antagonist, 0.6 mg/kg/day, i.p), both treatments, or vehicles for the last two weeks. Blood pressure, lipid profile, and glycemic control were evaluated. Histopathological examination, circulating cardiac troponin I (c-TnI), proinflammatory interleukin-6 (IL-6), apoptosis (active caspase-3 and Fas-immunostaining), interstitial fibrosis [transforming growth factor-ß1 (TGF-ß1), Mallory's trichrome staining], and extracellular matrix remodeling [matrix metalloproteinase-9 (MMP-9)], were used to assess cardiac pathology. Cardiac NR4A2 and its downstream factor, p53, as well as autophagic flux markers, SQSTM1/p62, LC3, and Beclin-1 were also determined. KEY FINDINGS: Moxonidine significantly ameliorated MetS-induced metabolic and hemodynamic derangements and the associated cardiac pathology. Moxonidine restored NR4A2 and p53 myocardial levels and enhanced autophagic flux via modulating SQSTM1/p62, LC3, and Beclin-1. Efaroxan reversed the majority of the moxonidine-induced improvements. SIGNIFICANCE: The current study suggests that autophagy modulation via I1R activation is involved in moxonidine-mediated cardiac beneficial effects in MetS.

Current advances on the therapeutic potential of pinocembrin: An updated review.

Pinocembrin (5,7-dihydroxyflavone) is a major flavonoid found in many plants, fungi and hive products, mainly honey and propolis. Several in vitro and preclinical studies revealed numerous pharmacological activities of pinocembrin including antioxidant, anti-inflammatory, antimicrobial, neuroprotective, cardioprotective and anticancer activities. Here, we comprehensively review and critically analyze the studies carried out on pinocembrin. We also discuss its potential mechanisms of action, bioavailability, toxicity, and clinical investigations. The wide therapeutic window of pinocembrin makes it a promising drug candidate for many clinical applications. We recommend some future perspectives to improve its pharmacokinetic and pharmacodynamic properties for better delivery that may also lead to new therapeutic advances.

Chemical profiling and dermatological and anti-aging properties of Syzygium jambos L. (Alston): evidence from molecular docking, molecular dynamics, and in vitro experiments.

The phytoconstituents of the aqueous extract from Syzygium jambos L. (Alston) leaves were defined using HPLC-PDA-MS/MS and the antioxidant, anti-aging, antibacterial, and anti-biofilm activities of the extract were in silico and in vitro investigated. The antioxidant activities were performed using in vitro DPPH and FRAP assays as well as H2-DCFDA assay in HaCaT cells in which oxidative stress was induced by UVA radiation. Anti-aging activity was tested in vitro, using aging-related enzymes. The antibacterial, anti-biofilm and inhibitory effects on bacterial mobilities (swarming and swimming) were assessed against Pseudomonas aeruginosa. Results showed that S. jambos aqueous extract contained 28 phytochemicals belonging to different metabolite classes, mainly phenolic acids, gallic acid derivatives, flavonoids, and ellagitannins. Mineral content analysis showed that S. jambos leaves contained moderate amounts of nitrogen, potassium, manganese, magnesium, and zinc, relatively low amounts of phosphorus and copper, and high concentration of calcium and iron. The extract displayed strong antioxidant activities in vitro and inhibited UVA-induced oxidative stress in HaCaT cells. Docking the major compounds identified in the extract into the four main protein targets involved in skin aging revealed an appreciable inhibitory potential of these compounds against tyrosinase, elastase, hyaluronidase, and collagenase enzymes. Moreover, molecular dynamic simulations were adopted to confirm the binding affinity of some selected compounds towards the target enzymes. The extract exhibited pronounced in vitro anti-aging effects, compared to kojic acid and quercetin (the reference compounds). It also inhibited the growth of P. aeruginosa, counteracted its ability to form biofilm, and impeded its swarming and swimming mobilities. Altogether, these findings strongly propose S. jambos leaves as a promising source of bioactive metabolites for the development of natural cosmeceutical and dermatological agents.

Vasorelaxant Effects of Syzygium samarangense (Blume) Merr. and L.M.Perry Extract Are Mediated by NO/cGMP Pathway in Isolated Rat Thoracic Aorta.

Syzygium samarangense (Blume) Merr. and L.M.Perry is utilized widely in traditional medicine. We have reported previously a wide array of pharmacological properties of its leaf extract, among them anti-inflammatory, antioxidant, hepatoprotective, antidiabetic, antiulcer, and antitrypanosomal activities. We also annotated its chemical composition using LC-MS/MS. Here, we continue our investigations and evaluate the vasorelaxant effects of the leaf extract on aortic rings isolated from rats and explore the possible underlying mechanisms. S. samarangense extract induced a concentration dependent relaxation of the phenylephrine-precontracted aorta in the rat model. However, this effect disappeared upon removing the functional endothelium. Pretreating the aortic tissues either with propranolol or NG-nitro-L-arginine methyl ester inhibited the relaxation induced by the extract; however, atropine did not affect the extract-induced vasodilation. Meanwhile, adenylate cyclase inhibitor, MDL; specific guanylate cyclase inhibitor, ODQ; high extracellular KCl; and indomethacin as cyclooxygenase inhibitor inhibited the extract-induced vasodilation. On the other hand, incubation of S. samarangense extract with aortae sections having their intact endothelium pre-constricted using phenylephrine or KCl in media free of Ca2+ showed no effect on the constriction of the aortae vessels induced by Ca2+. Taken together, the present study suggests that S. samarangense extract dilates isolated aortic rings via endothelium-dependent nitric oxide (NO)/cGMP signaling. The observed biological effects could be attributed to its rich secondary metabolites. The specific mechanisms of the active ingredients of S. samarangense extract await further investigations.

Black pepper oil (Piper nigrum L.) mitigates dexamethasone induced pancreatic damage via modulation of oxidative and nitrosative stress.

Dexamethasone acts as an immunosuppressive drug and has been used recently in the management of specific coronavirus disease 2019 (COVID-19) cases; however, various adverse effects could limit its use. In this work, we studied the mitigation effects of black pepper oil (BP oil) on glycemic parameters, dyslipidemia, oxidative and nitrosative stress and pancreatic fibrosis in dexamethasone-treated rats. Animals were divided into five groups that were treated with vehicle, dexamethasone (10 mg/kg, SC) or black pepper oil (BP oil, 0.5 mL, or 1 mL/kg) or metformin (50 mg/kg) plus dexamethasone for 4 consecutive days. Serum insulin, blood glucose, total cholesterol, triglycerides, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were higher in the dexamethasone group vs the control group and decreased in BP oil and metformin groups relative to the dexamethasone group. Pancreatic nitric oxide, inducible nitric oxide synthase and malondialdehyde levels were increased in the dexamethasone group vs the control group and decreased in BP oil and metformin groups relative to the dexamethasone group. Pancreatic endothelial nitric oxide synthase and reduced glutathione were declined in the dexamethasone group vs the control group. They were increased in BP oil and metformin groups relative to the dexamethasone group. Moreover, the pancreatic islets diameter and collagen deposition were assessed and found to be higher in the dexamethasone group vs the control group. BP oil and metformin groups showed to regress this effect. In conclusion, BP oil may alleviate hyperglycemia, hyperinsulinemia, insulin resistance, dyslipidemia and pancreatic structural derangements and fibrosis by suppressing oxidative stress, increasing endogenous antioxidant levels, modulating nitric oxide signaling, preventing pancreatic stellate cells transition and collagen deposition.

Carvedilol ameliorates dexamethasone-induced myocardial injury in rats independent of its action on the α1-adrenergic receptor.

The current study aimed to investigate the cardiotoxic effect of dexamethasone-high-dose in rats, the therapeutic effect of carvedilol and the role of α1-adrenergic receptor (α1AR). The experiment involved 6 groups: control, dexamethasone (10 mg/kg), carvedilol (10 mg/kg), phenylephrine (1 mg/kg), phenylephrine plus carvedilol and propranolol (30 mg/kg). Drugs and vehicles were given for 7 days. Dexamethasone was given with the drugs in the last 4 groups. On the 8th-day and after overnight fasting, serum and cardiac samples were collected. Serum levels of cardiac troponin I and creatine kinase-myoglobin as well as cardiac levels of diacylglycerol, malondialdehyde, kinase activity of Akt, transforming growth factor-ß, Smad3 and alpha smooth muscle actin were measured. Cardiac samples were also used for histopathological examination using hematoxylin-eosin and Sirius red stains, in addition to immunohistochemical examination using ß-arrestin2 antibody. Dexamethasone induced cardiac injury via increasing oxidative stress, apoptosis and profibrotic signals. Carvedilol significantly reduced the dexamethasone-induced cardiotoxicity. Using phenylephrine, a competitive α1-agonist, with carvedilol potentiated the cardioprotective actions of carvedilol. Propranolol, a ß-blocker without activity on α1ARs, showed higher cardiac protection than carvedilol. Dexamethasone-high-dose upregulates cardiac oxidative stress, apoptotic and profibrotic signals and induces cardiac injury. Blocking the α1-adrenergic receptor by carvedilol attenuates its cardioprotective effects against dexamethasone-induced cardiotoxicity.

Curcuminoids for Metabolic Syndrome: Meta-Analysis Evidences Toward Personalized Prevention and Treatment Management.

The metabolic syndrome (MS) is a multifactorial syndrome associated with a significant economic burden and healthcare costs. MS management often requires multiple treatments (polydrug) to ameliorate conditions such as diabetes mellitus, insulin resistance, obesity, cardiovascular diseases, hypertension, and non-alcoholic fatty liver disease (NAFLD). However, various therapeutics and possible drug-drug interactions may also increase the risk of MS by altering lipid and glucose metabolism and promoting weight gain. In addition, the medications cause side effects such as nausea, flatulence, bloating, insomnia, restlessness, asthenia, palpitations, cardiac arrhythmias, dizziness, and blurred vision. Therefore, is important to identify and develop new safe and effective agents based on a multi-target approach to treat and manage MS. Natural products, such as curcumin, have multi-modalities to simultaneously target several factors involved in the development of MS. This review discusses the recent preclinical and clinical findings, and up-to-date meta-analysis from Randomized Controlled Trials regarding the effects of curcumin on MS, as well as the metabonomics and a pharma-metabolomics outlook considering curcumin metabolites, the gut microbiome, and environment for a complementary personalized prevention and treatment for MS management.

Unraveling the Phytochemistry, Traditional Uses, and Biological and Pharmacological Activities of Thymus algeriensis Boiss. & Reut.

Growing concern for public health has increased the need to change the paradigm towards a healthcare system that advocates holistic practices while reducing adverse effects. Herbal therapy is becoming an integral part of the therapeutic arsenal, and several successful plant-derived compounds/molecules are being introduced into the market. The medicinal plants belonging to the genus Thymus are among the most important species within the Lamiaceae family. One of them is Thymus algeriensis which is mainly distributed in the Mediterranean region. For a long time, this species has been used in traditional medicine to treat several disorders and diseases including inflammation, diabetes, rheumatism, digestive, and respiratory affections. This review describes the traditional uses, phytochemical composition, and biological and pharmacological activities of T. algeriensis extracts. Data were obtained using electronic databases such as SciFindern, ScienceDirect, Scopus, and Web of Science. Several plant-based extracts and a broad spectrum of identified secondary metabolites were highlighted and discussed with respective activities and modes of action. T. algeriensis represents a promising natural resource for the pharmaceutical industry mainly for antioxidant, anti-inflammatory, antimicrobial, and anticancer activities. Considering these findings, more research is needed to transmute the conventional uses of T. algeriensis into scientifically sound information. Moreover, extensive preclinical, clinical, toxicological, and pharmacokinetic trials on this species and its derivatives compounds are required to underpin the mechanisms of action and ensure its biosafety and efficiency. This comprehensive review provides a scientific basis for future investigations on the use of T. algeriensis and derived compounds in health maintenance and promotion and disease prevention.

Watery Rose Apple: A Comprehensive Review of Its Traditional Uses, Nutritional Value, Phytochemistry, and Therapeutic Merits against Inflammation-Related Disorders.

The myrtle family, Myrtaceae, constitutes over 5500 species, and Syzygium is considered the largest genus of the flowering plants within the family. The watery rose apple, Syzygium aqueum, is a traditional medicinal plant with various bioactive compounds distributed in all plant parts. These include phenolic compounds, flavonoids, tannins, terpenoids, and essential oils. S. aqueum extracts and their isolated compounds showed multiple beneficial biological effects such as antibacterial, antifungal, antidiabetic, analgesic, antimalarial, antioxidant, anti-inflammatory, and anticancer activities. This review is aimed at discussing all the available information about the nutritional value, traditional uses, and therapeutic properties of the leaves, fruit, and stem bark of the plant, in addition to the distribution of phytoconstituents in its different parts as well as recommend future research directions on this species to promote its clinical uses.

Coriander Oil Reverses Dexamethasone-Induced Insulin Resistance in Rats.

In the present study, we aimed to investigate the effect of coriander oil on dexamethasone-induced insulin resistance in rats and characterize its chemical composition using gas chromatography-mass spectrometry (GC-MS). Rats were divided into five groups (n = 6): Normal control, insulin resistance (IR) control, IR + metformin (50 mg/kg/day, PO, Per Oral), IR + coriander oil low dose (0.5 mL/kg, PO), and IR + coriander oil high dose (1 mL/kg, PO). IR groups were injected with a dose of 10 mg/kg dexamethasone subcutaneously for four consecutive days. All groups received either vehicle or drugs daily for four days. Animal weights and pancreatic weights were measured, and oral glucose tolerance test was performed at the end of study. Fasting glucose, triglycerides (TG), total cholesterol (TC), HDL and insulin levels in serum, MDA, and GSH levels in pancreatic tissue were measured and HOMA-IR was calculated. Immunoexpression of apoptosis markers BAX, and BCL2 was measured in pancreatic tissues and BAX/BCL2 ratio was calculated. Histopathological examination of pancreatic tissues was also performed. Pancreatic weight, serum HDL, pancreatic GSH, and BCL2 were decreased while serum glucose, insulin, TG, TC levels, AUC of OGGT, HOMA-IR, pancreatic MDA, BAX, and BAX/BCL2 ratio were increased in IR rats. Histopathological examination showed congestion, vacuolation and hemorrhage in pancreatic islets. These changes were reversed by metformin and the high dose of coriander oil treatments. The obtained activities could be attributed to the presence of 21 volatile compounds, identified by GC-MS. Our study indicates that coriander oil can be used as an adjuvant antihyperglycemic agent in type 2 diabetes. Further experiments are needed to determine the therapeutic dose and the treatment time.

Pentagalloyl Glucose, a Major Compound in Mango Seed Kernel, Exhibits Distinct Gastroprotective Effects in Indomethacin-Induced Gastropathy in Rats via Modulating the NO/eNOS/iNOS Signaling Pathway.

Gastric ulcers are a common health disorder that affect up to 10% of the world's population. The gastroprotective potential of pentagalloyl glucose (PGG) against indomethacin-induced ulcer in rats and the possible underlying mechanisms were investigated. Gastric ulceration was induced by indomethacin (single dose, 60 mg/kg). Pretreatment with PGG (100 or 200 mg/kg, orally) for 8 days prior to the administration of indomethacin furnished significant reductions in gastric mucosal lesions as well as a significant increase in mucus concentration. Also, PGG significantly declined the elevations in gastric mucosal MDA, TNF-α, IL-6, PECAM-1, VEGF, and iNOS expression. It also mitigated the decrease in GSH and GPx and eNOS expression observed with indomethacin. The protective effects furnished by PGG were comparable to that of famotidine. The obtained results suggested that the anti-ulcer effects of PGG are mediated by increasing mucus production, scavenging free radicals, decreasing inflammation, and attenuating the NO/NOS signaling in favor of eNOS. To sum up, PGG could provide a potential therapy for gastric ulcer after evaluating its efficacy and effectiveness.