Molecular docking analysis of AGTR1 antagonists.

Cardiovascular diseases (CVDs) are the leading cause of death and morbidity globally. The renin-angiotensin system is an important regulatory system for maintaining cardiovascular and renal function. Therefore, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have emerged as first-line treatments for conditions such as hypertension and heart failure. Currently available synthetic medications used to treat various CVDs have been linked with various adverse effects. Therefore, this study focuses on targeting type-1 angiotensin II receptor (AGTR1) by natural compounds. The ZINC database natural compounds and standard AGTR1 inhibitors have been screened against the AGTR1 active site. The results showed that five compounds, namely ZINC85625504, ZINC62001623, ZINC70666587, ZINC06624086, and ZINC95486187, had similar binding energies to established AGTR1 inhibitors. These compounds were found to interact with crucial AGTR1 residues, indicating their potential as AGTR1 inhibitors. Moreover, the hit compounds demonstrated favorable drug-like characteristics and warrant further investigation for their potential use in managing CVD.

Combination of sweet orange, lentisk and lemon eucalyptus essential oils: Optimization of a new complete antimicrobial formulation using a mixture design methodology.

Sweet orange (Citrus × sinensis (L.) Osbeck), lentisk (Pistacia lentiscus L.) and lemon eucalyptus (Eucalyptus citriodora Hook) are medicinal plants known by its culinary virtues. Their volatile oils have demonstrated promising antimicrobial activity against a panel of microbial strains, including those implicated in food deterioration. In this exploratory investigation, we aimed to determine the antimicrobial formulation of sweet orange, lentisk and lemon eucalyptus essential oils (EOs) using the simplex-centroid mixture design approach coupled with a broth microdilution method. EOs were first extracted by hydrodistillation, and then their phytochemical profile was characterized using Gas chromatography-mass spectrometry (GC-MS). GC-MS analysis identified d-limonene (14.27%), careen-3 (14.11%), ß-myrcene (12.53%) as main components of lentisk EOs, while lemon eucalyptus was dominated by citronellal (39.40%), ß-citronellol (16.39%) and 1,8-cineole (9.22%). For sweet orange EOs, d-limonene (87.22%) was the principal compound. The three EOs exhibited promising antimicrobial potential against various microorganisms. Lemon eucalyptus and sweet orange EO showed high activity against most tested microorganisms, while lentisk EO exerted important effect against some microbes but only moderate activity against others. The optimization formulations of antimicrobial potential showed interesting synergistic effects between three EOs. The best combinations predicted on C. albicans, S. aureus, E. coli, S. enterica and B. cereus correspond to 44%/55%/0%, 54%/16%/28%, 43%/22%/33%, 45%/17%/36% and 36%/30%/32% of Citrus sinensis, Pistacia lentiscus and Eucalyptus citriodora EOs, respectively. These findings suggest that the combination of EOs could be used as natural food preservatives and antimicrobial agents. However, further studies are needed to determine the mechanisms of action and efficacy of these EOs against different microorganisms.

Phytochemical, Antidiabetic, Antioxidant, Antibacterial, Acute and Sub-Chronic Toxicity of Moroccan Arbutus unedo Leaves.

Objectives: Moroccan Arbutus unedo is an essential medicinal plant; however, little is known about the biological properties of its leaves mentioned in Moroccan traditional medicine. Methods: Various standard experiments were performed to evaluate the phytochemical, antidiabetic, antioxidant, antibacterial, and acute and sub-chronic toxicity characteristics of A. unedo leaves. Results: Phytochemical screening led to the identification of several phytochemical classes, including tannins, flavonoids, terpenoids, and anthraquinones, with high concentrations of polyphenols (31.83 ± 0.29 mg GAEs/g extract) and flavonoids (16.66 ± 1.47 mg REs/g extract). Further, the mineral analysis revealed high levels of calcium and potassium. A. unedo extract demonstrated significant antioxidant and anti-diabetic activities by inhibiting α-amylase (1.350 ± 0.32 g/mL) and α-glucosidase (0.099 ± 1.21 g/mL) compared to the reference drug Acarbose. Also, the methanolic extract of the plant exhibited significantly higher antibacterial activity than the aqueous extract. Precisely, three of the four examined bacterial strains exhibited substantial susceptibility to the methanolic extract . Minimum bactericidal concentration (MBC)/minimum inhibitory concentration (MIC) values indicated that A. unedo harbor abundant bactericidal compounds. For toxicological studies, mice were administered with A. unedo aqueous extract at single doses of 2,000 and 5,000 mg/kg. They did not exhibit significant abnormal behavior, toxic symptoms, or death during the 14-day acute toxicity test and the 90-day sub-chronic toxicity test periods. The general behavior, body weight, and hematological and biochemical status of the rats were assessed, revealing no toxicological symptoms or clinically significant changes in biological markers observed in the mice models, except hypoglycemia, after 90 days of daily dose administration. Conclusion: The study highlighted several biological advantages of A. unedo leaves without toxic effects in short-term application. Our findings suggest that conducting more comprehensive and extensive in vivo investigations is of utmost importance to identify molecules that can be formulated into pharmaceuticals in the future.

Determination of Chemical Composition and Investigation of Biological Activities of Ocimum basilicum L.

This study aimed to determine the chemical composition of the essential oils (EOs) of Ocimum basilicum L., as well as to evaluate the antibacterial, antidiabetic, dermatoprotective, and anti-inflammatory properties, and the EOs and aqueous extracts of O. basilicum. The antibacterial activity was evaluated against bacterial strains, Gram-positive and Gram-negative, using the well diffusion and microdilution methods, whereas the antidiabetic activity was assessed in vitro using two enzymes involved in carbohydrate digestion, α-amylase and α-glucosidase. On the other hand, the dermatoprotective and anti-inflammatory activities were studied by testing tyrosinase and lipoxygenase inhibition activity, respectively. The results showed that the chemical composition of O. basilicum EO (OBEO) is dominated by methyl chavicol (86%) and trans-anethol (8%). OBEO exhibited significant antibacterial effects against Gram-negative and Gram-positive strains, demonstrated by considerable diameters of the inhibition zones and lower MIC and MBC values. In addition, OBEO exhibited significant inhibition of α-amylase (IC50 = 50.51 ± 0.32 µg/mL) and α-glucosidase (IC50 = 39.84 ± 1.2 µg/mL). Concerning the anti-inflammatory activity, OBEO significantly inhibited lipoxygenase activity (IC50 = 18.28 ± 0.03 µg/mL) compared to the aqueous extract (IC50 = 24.8 ± 0.01 µg/mL). Moreover, tyrosinase was considerably inhibited by OBEO (IC50 = 68.58 ± 0.03 µg/mL) compared to the aqueous extract (IC50 = 118.37 ± 0.05 µg/mL). The toxicological investigations revealed the safety of O. basilicum in acute and chronic toxicity. The finding of in silico analysis showed that methyl chavicol and trans-anethole (main compounds of OBEO) validate the pharmacokinetics of these compounds and decipher some antibacterial targets.

Hypertrophic Cardiomyopathy in Saudi Arabia: A Systematic Review of the Epidemiological, Clinical, and Imaging Features.

BACKGROUND: A systematic review was performed to deliver a critical view of clinical and research practice on hypertrophic cardiomyopathy (HCM) in Saudi Arabia. Scopus, PubMed, and Google Scholar databases were searched for original articles reporting clinical and/or imaging findings among HCM patients in Saudi Arabia. Of 559 records identified, 3 studies and 1 abstract were included, involving 169 patients. METHODS: The mean age ranged between 40and 56 years, up to 93.3% were males. A family history of HCM was reported in one study (5%), and sudden cardiac death was investigated in two studies (9% and 13%). Dyspnea was the most frequent symptom (60-68.7%) reported, followed by chest pain (12.5%-73.3%). RESULTS: Regarding complications, atrial fibrillation was reported among 0-25% of the patients, mitral regurgitations among 13.3-50%, and ventricular tachycardia among 5-12.5%. Imaging parameters were inadequately documented and suggested a high prevalence of left atrial enlargement, SVI + RV5 > 35 mm, blocks, and asymmetric septal hypertrophy. CONCLUSION: The ejection fraction was reported by two studies with a mean±SD of 68±13% and 77.2±8.07%. The researchers stress the paucity, low quality, and disparity in time of original studies about HCM in Saudi Arabia and recommend conducting national multicenter studies, with appropriate design, notably using screening-based recruitment methods.

Antioxidative and Anti-Inflammatory Protective Effects of ß-Caryophyllene against Amikacin-Induced Nephrotoxicity in Rat by Regulating the Nrf2/AMPK/AKT and NF-κB/TGF-ß/KIM-1 Molecular Pathways.

Herein, the molecular pathogenic pathways implicated in renal injury triggered by amikacin (AK), together with the alleviating actions of ß-caryophyllene (BCP), were investigated. Adult male Wistar rats (n = 32) were disseminated to the four following groups (n = 8/group): normal group, positive control animals (PC) that received AK intraperitoneal injections for 14 days (500 mg/kg/day), and rats that received AK simultaneously with small (200 mg/kg/day) and high doses (400 mg/kg/day) of BCP. The PC renal tissues revealed abnormal histology alongside increased apoptosis and significantly elevated serum creatinine and urea with marked proteinuria and oliguria relative to the normal rats. Moreover, renal tissues from the PC animals also showed substantial upregulations in NF-κB/TGF-ß/KIM-1, whilst Nrf2/AMPK/AKT/PCNA declined, at the gene and protein levels in comparison to the normal rats. Additionally, the levels of markers of oxidative stress (MDA/H2O2/protein adducts) and inflammation (TNF-α/IL-1ß/IL-6/IL-18/TLR/HSP25) were substantially higher in the PC renal specimens, whereas the antioxidants (GSH/GPx/SOD1/CAT) and interleukin-10 decreased, relative to the NC group. Both BCP protocols improved the biochemical markers of renal functions, alleviated renal histopathology and apoptosis, and decreased NF-κB/TGF-ß/KIM-1 alongside the concentrations of oxidative stress and proinflammatory markers, whilst promoting Nrf2/AMPK/AKT/IL-10/PCNA and the targeted antioxidants. However, the improving effects in the high-dose regimen were markedly stronger than those observed in animals treated with low dose of BCP. In conclusion, the present report is the first to connect NF-κB/TGF-ß/KIM-1 proinflammatory and Nrf2/AMPK/AKT antioxidative stress pathways with the pathogenesis of AK-induced nephrotoxicity. Additionally, the current report is the first to disclose alleviating activities for BCP against AK-triggered nephrotoxicity by modulating multiple antioxidative stress with anti-inflammatory molecular pathways.

Effects of Resveratrol Against Induced Metabolic Syndrome in Rats: Role of Oxidative Stress, Inflammation, and Insulin Resistance.

Metabolic syndrome (MS) is a serious health problem associated with an increase in risk factors for hepatic steatosis, which is the most common liver disease today. The goal of this study was to investigate the protective effects of resveratrol against metabolic alterations associated with a high-fat high-fructose diet (HFFD). Thirty-two male rats were randomly divided into four equal groups: control (cont.), metabolic syndrome (MS), resveratrol (Res), and metabolic syndrome treated with resveratrol (MS + Res). Resveratrol was administrated orally at a dose of 30 mg/kg·bw, daily. After 10 weeks, body weight, serum biochemical parameters, hepatic oxidative stress, inflammatory markers, as well as mRNA levels of hepatic genes related to lipid metabolism and insulin signaling were measured. In addition, the liver was examined histopathologically to detect lipid deposition. Increased body weight, hepatic dysfunction, dyslipidemia, hepatic insulin resistance, hepatic oxidative and inflammatory stress conditions, upregulation of mRNA expression level of sterol regulatory element binding protein 1-c (SREBP1-c), and downregulation of mRNA expression levels of peroxisome proliferated activated receptor alpha (PPARα) and insulin receptor substrate-2 (IR-S2) were all observed in the MS rats. Hepatic steatosis was confirmed by hematoxylin and eosin and Oil Red O staining. Administration of resveratrol reduced liver steatosis, oxidative stress, and inflammatory state. Also, it improved lipid profile as well as insulin sensitivity and reverted alterations in hepatic mRNA expression levels of the tested genes. Based on these findings, resveratrol could be proposed as a therapeutic approach for MS prevention.

Singular and Combined Effects of Essential Oil and Honey of Eucalyptus Globulus on Anti-Inflammatory, Antioxidant, Dermatoprotective, and Antimicrobial Properties: In Vitro and In Vivo Findings.

Eucalyptus globulus is a plant widely used by the world population, including Morocco, in the treatment of several pathologies. The aim of this work is to evaluate the antioxidant, anti-inflammatory, dermatoprotective, and antimicrobial effects of essential oil and honey from E. globulus, as well as their combination. Chemical composition was determined by GC-MS analysis. The antioxidant activity was evaluated by three tests, namely, DPPH, reducing power, and the ß-carotene/linoleic acid assay. The anti-inflammatory activity was investigated in vitro (5-lipoxygenase inhibition) and in vivo (carrageenan-induced paw edema model), while the dermatoprotective activity was tested in vitro (tyrosinase inhibition). Moreover, the antibacterial activity was assessed using agar well diffusion and microdilution methods. The results showed that eucalyptol presents the main compound of the essential oil of E. globulus (90.14%). The mixture of essential oil with honey showed the best antioxidant effects for all the tests used (0.07 < IC50 < 0.19 mg/mL), while the essential oil was the most active against tyrosinase (IC50 = 38.21 ± 0.13 µg/mL) and 5-lipoxygenase (IC50 = 0.88 ± 0.01 µg/mL), which corroborated the in vivo test. Additionally, the essential oil showed the best bactericidal effects against all strains tested, with inhibition diameter values ranging from 12.8 to 21.6 mm. The findings of this work showed that the combination of the essential oil with honey showed important results in terms of biological activity, but the determination of the underlying mechanisms of action remains a major prospect to be determined.

Chemical Analysis and Investigation of Biological Effects of Salvia officinalis Essential Oils at Three Phenological Stages.

Salvia officinalis is a medicinal plant used to treat some diseases, including microbial infections and diabetes. Different studies showed the biological and pharmacological properties of this species. The aim of this study was the determination of the chemical compounds of S. officinalis essential oils and the investigation of their antimicrobial, antioxidant, antidiabetic, and anti-inflammatory properties. The chemical compounds of S. officinalis were determined by GC-MS analysis. The antioxidant activity was assessed by DPPH, ABTS, H2O2, and FRAP assays. The in vitro antidiabetic effect was evaluated by the inhibition of α-amylase, α-glucosidase, and lipase activities, and the anti-inflammatory effect was evaluated using the 5-lipoxygenase assay. Moreover, antibacterial activity was assessed against six bacterial strains using agar well diffusion assay and microdilution method. The main compounds in essential oils of S. officinalis at three phenological stages were naphthalenone, camphor, 1.8-cineole, and α-thujone. The full flowering stage essential oil showed the best antioxidant activity with different IC50 values according to the used tests. This oil also exhibited important inhibitory effects at the full flowering stage against α-amylase (IC50 = 69.23 ± 0.1 µg/mL), α-glucosidase (IC50 = 22.24 ± 0.07 µg/mL), and lipase (IC50 = 37.3 ± 0.03 µg/mL). The 5-lipoxygenase inhibitory effect was the best at the full flowering stage (IC50 = 9.24 ± 0.03 µg/mL). The results of the antibacterial evaluation revealed that, at three seasonal periods, S. officinalis essential oil demonstrated strong antibacterial activity. Although the full flowering stage had the best antibacterial activity, there were no significant differences between the three stages. Additionally, the essential oils showed bactericidal effects on Listeria monocytogenes, Staphylococcus aureus, Bacillus subtilis, Proteus mirabilis, Escherichia coli, and Salmonella typhimurium, respectively. The findings of this work showed remarkably that S. officinalis synthesizes essential oils according to different developmental stages. Moreover, it has exhibited interesting biological and pharmacological properties justifying its medicinal effects and suggesting it as a very important source of natural drugs.

A Computational Approach to Elucidate the Interactions of Chemicals From Artemisia annua Targeted Toward SARS-CoV-2 Main Protease Inhibition for COVID-19 Treatment.

The inhibitory potential of Artemisia annua, a well-known antimalarial herb, against several viruses, including the coronavirus, is increasingly gaining recognition. The plant extract has shown significant activity against both the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and the novel SARS-CoV-2 that is currently ravaging the world. It is therefore necessary to evaluate individual chemicals of the plant for inhibitory potential against SARS-CoV-2 for the purpose of designing drugs for the treatment of COVID-19. In this study, we employed computational techniques comprising molecular docking, binding free energy calculations, pharmacophore modeling, induced-fit docking, molecular dynamics simulation, and ADMET predictions to identify potential inhibitors of the SARS-CoV-2 main protease (Mpro) from 168 bioactive compounds of Artemisia annua. Rhamnocitrin, isokaempferide, kaempferol, quercimeritrin, apigenin, penduletin, isoquercitrin, astragalin, luteolin-7-glucoside, and isorhamnetin were ranked the highest, with docking scores ranging from -7.84 to -7.15 kcal/mol compared with the -6.59 kcal/mol demonstrated by the standard ligand. Rhamnocitrin, Isokaempferide, and kaempferol, like the standard ligand, interacted with important active site amino acid residues like HIS 41, CYS 145, ASN 142, and GLU 166, among others. Rhamnocitrin demonstrated good stability in the active site of the protein as there were no significant conformational changes during the simulation process. These compounds also possess acceptable druglike properties and a good safety profile. Hence, they could be considered for experimental studies and further development of drugs against COVID-19.

Crocus sativus L. Tepal Extract Induces Apoptosis in Human U87 Glioblastoma Cells.

Crocus sativus (C. sativus) is considered as the costliest spice and an important medicinal plant. Herein, we investigated the effects of tepal extract (TE) of C. sativus on the viability of the human glioblastoma cells. Results revealed that TE significantly (P < 0.05) inhibited the proliferation of U87 glioblastoma cells in a dose-dependent manner with comparatively lower toxic effects against normal astrocytes. The IC50 of TE against U87 glioblastoma cells was found to be 130 µg/mL as compared to 600 µg/mL against normal astrocytes. TE also inhibited the colony formation of U87 cells significantly (P < 0.05). The AO/EB and Annexin V/PI staining assays indicated that TE stimulated apoptosis in U87 cells dose dependently. The early and late apoptotic U87 cells increased from 0.66% and 2.3% at control to 14.2% and 21.4% at 260 µg/mL of TE. Moreover, TE caused upregulation of Bax and suppression of Bcl-2. Wound healing assay showed that migration of the U87 cells was suppressed significantly (P < 0.05) at 80 µg/mL of TE. Taken together, these results suggest that TE exhibits antiproliferative effects against U87 glioma cells and may prove to be an important source of natural anticancer agents.

Salvadora persica extract attenuates cyclophosphamide-induced hepatorenal damage by modulating oxidative stress, inflammation and apoptosis in rats.

OBJECTIVE: Salvadora persica (SP) is used as a food additive and is a common ingredient in folk medicine. This study investigates the antioxidant, anti-inflammatory, and beneficial effects of SP against cyclophosphamide (CYP) toxicity in rats. METHODS: In a 10-day study, 32 male rats were equally allocated into 4 groups (8 rats/group) as follows: the normal control (NC group), normal rats that only received oral aqueous extract of SP (100 mg/[kg·d]; SP group), animals treated with intraperitoneal CYP injections (30 mg/[kg·d]; CYP group), and the CYP + SP group that concurrently received CYP with SP aqueous extract. Serum samples were collected to measure the liver and renal biochemical profiles, as well as antioxidant and oxidative stress markers and the concentrations of interleukin-1ß (IL-1ß), IL-6, IL-10, tumor necrosis factor-α (TNF-α), nuclear factor-κB (NF-κB) and adenosine 5'-monophosphate-activated protein kinase (AMPK). Hepatic and renal tissues were also harvested for histopathology and to measure apoptosis using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling technique, alongside tissue levels of oxidative stress markers. RESULTS: Liver enzymes, total bilirubin, creatinine and urea, as well as serum IL-1ß, IL-6, TNF-α and NF-κB increased significantly, whilst total protein, albumin, calcium, IL-10 and AMPK declined in serum of the CYP group relative to the NC group. The hepatorenal concentrations of glutathione, glutathione peroxidase and catalase declined markedly in the CYP group, whereas malondialdehyde, protein adducts, and apoptosis index increased compared with the NC group. By contrast, the hepatorenal biochemistry and apoptosis index of the SP group were comparable to the NC group. Interestingly, the CYP + SP group had significant improvements in the liver and renal biochemical parameters, enhanced anti-oxidative and anti-inflammatory effects, and marked declines in hepatic and renal apoptosis relative to the CYP group. Moreover, all monitored parameters were statistically indistinguishable between the CYP + SP group and the NC group. CONCLUSION: This study suggests that the aqueous extract of SP could be a potential remedy against CYP-induced hepatorenal damage and may act by modulating the AMPK/NF-κB signaling pathway and promoting anti-oxidative and anti-inflammatory activities.

Flavonoids a Bioactive Compound from Medicinal Plants and Its Therapeutic Applications.

Plants generally secrete secondary metabolites in response to stress. These secondary metabolites are very useful for humankind as they possess a wide range of therapeutic activities. Secondary metabolites produced by plants include alkaloids, flavonoids, terpenoids, and steroids. Flavonoids are one of the classes of secondary metabolites of plants found mainly in edible plant parts such as fruits, vegetables, stems, grains, and bark. They are synthesized by the phenylpropanoid pathway. Flavonoids possess antibacterial, antiviral, antioxidant, anti-inflammatory, antimutagenic, and anticarcinogenic properties. Due to their various therapeutic applications, various pharmaceutical companies have exploited different plants for the production of flavonoids. To overcome this situation, various biotechnological strategies have been incorporated to improve the production of different types of flavonoids. In this review, we have highlighted the various types of flavonoids, their biosynthesis, properties, and different strategies to enhance the production of flavonoids.

In Vitro Alpha-Amylase Enzyme Assay of Hydroalcoholic Polyherbal Extract: Proof of Concept for the Development of Polyherbal Teabag Formulation for the Treatment of Diabetes.

For the treatment and maintenance of postprandial blood glucose increases (i.e., diabetes mellitus), alpha (α)-amylase is a well-known therapeutic target. In this paper, we report an initial exploration of the work, i.e., in vitro alpha-amylase activity of the hydroalcoholic polyherbal extract of the selected plants. After drying, the plant material is ground individually, and at least 100 gm of the crude powder is prepared from each plant. 100 gm of each plant was combined, and a total of 500 gm of the crude powder (Ichnocarpus frutescens (100 gm) + Ficus dalhousie (100 gm) + Crateva magna (100 gm) + Alpinia galangal (100 gm) + Swertia chirata (100 gm)) was prepared to carry out the extraction. This obtained extract was subjected to preliminary phytochemical screening and in vitro alpha-amylase activity. At 16 mg/mL, acarbose displayed 78.40 ± 0.36% inhibition, whereas the extract exhibited 72.96 ± 0.70% inhibition, which is significantly comparable. The IC50 value of acarbose was 12.9 ± 1.12, whereas the extract exhibited 13.31 ± 1.12 mg/mL. The extract possesses numerous classes of chemicals such as alkaloids, glycosides, tannins, polyphenols, and terpenoids, which can contribute to the antidiabetic activity through alpha-amylase inhibition. This was an initial exploration of the work as a proof of concept for the development of polyherbal tea bag formulation for the treatment of diabetes. In the future, we are aiming to investigate the effectiveness of polyherbal tea bags in the treatment of diabetes using more in vitro and in vivo models. From the present investigation, we have concluded that this extract can be used for the treatment of diabetes.

Frequency of Metabolic Syndrome and Study of Anthropometric, Clinical and Biological Characteristics in Peri- and Postmenopausal Women in the City of Ksar El Kebir (Northern Morocco).

This study aimed to determine the frequency of metabolic syndrome and to identify its predictive factors in peri- and post-menopausal women in the city of Ksar El Kebir, in northern Morocco. A total of 373 peri- and post-menopausal women between 45 and 64 years old participated in the study. Metabolic syndrome was diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) definition. Body mass index (BMI) was calculated to assess the degree of obesity in women; anthropometric, clinical and biological parameters were collected during interviews. The mean ages of peri- and postmenopausal women were 48.84 ± 2.4 years and 56.65 ± 4.29 years, respectively. Postmenopausal women had higher means of anthropometric and biological parameters than peri-menopausal women. We also noted a predominance of metabolic syndrome in postmenopausal women (n = 158) compared to peri-menopausal women (n = 81). Waist circumference was the predominant marker in the subjects studied, whereas triglycerides were the lower marker. In the overall population, the incidence of metabolic syndrome and its associated factors were higher in postmenopausal women than in peri-menopausal women, from which it can be concluded that post menopause may be a predictor of metabolic syndrome.

Differential remodelling of mitochondrial subpopulations and mitochondrial dysfunction are a feature of early stage diabetes.

Mitochondrial dysfunction is a feature of type I and type II diabetes, but there is a lack of consistency between reports and links to disease development. We aimed to investigate if mitochondrial structure-function remodelling occurs in the early stages of diabetes by employing a mouse model (GENA348) of Maturity Onset Diabetes in the Young, exhibiting hyperglycemia, but not hyperinsulinemia, with mild left ventricular dysfunction. Employing 3-D electron microscopy (SBF-SEM) we determined that compared to wild-type, WT, the GENA348 subsarcolemma mitochondria (SSM) are ~ 2-fold larger, consistent with up-regulation of fusion proteins Mfn1, Mfn2 and Opa1. Further, in comparison, GENA348 mitochondria are more irregular in shape, have more tubular projections with SSM projections being longer and wider. Mitochondrial density is also increased in the GENA348 myocardium consistent with up-regulation of PGC1-α and stalled mitophagy (down-regulation of PINK1, Parkin and Miro1). GENA348 mitochondria have more irregular cristae arrangements but cristae dimensions and density are similar to WT. GENA348 Complex activity (I, II, IV, V) activity is decreased but the OCR is increased, potentially linked to a shift towards fatty acid oxidation due to impaired glycolysis. These novel data reveal that dysregulated mitochondrial morphology, dynamics and function develop in the early stages of diabetes.

Three-dimensional electron microscopy techniques for unravelling mitochondrial dysfunction in heart failure and identification of new pharmacological targets.

A hallmark of heart failure is mitochondrial dysfunction leading to a bioenergetics imbalance in the myocardium. Consequently, there is much interest in targeting mitochondrial abnormalities to attenuate the pathogenesis of heart failure. This review discusses (i) how electron microscopy (EM) techniques have been fundamental for the current understanding of mitochondrial structure-function, (ii) the paradigm shift in resolutions now achievable by 3-D EM techniques due to the introduction of direct detection devices and phase plate technology, and (iii) the application of EM for unravelling mitochondrial pathological remodelling in heart failure. We further consider the tremendous potential of multi-scale EM techniques for the development of therapeutics, structure-based ligand design and for delineating how a drug elicits nanostructural effects at the molecular, organelle and cellular levels. In conclusion, 3-D EM techniques have entered a new era of structural biology and are poised to play a pivotal role in discovering new therapies targeting mitochondria for treating heart failure. LINKED ARTICLES: This article is part of a themed section on Mitochondrial Pharmacology: Featured Mechanisms and Approaches for Therapy Translation. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.22/issuetoc.