Antioxidative hypoglycemic herbal medicines with in vivo and in vitro activity against C-reactive protein; a systematic review.

BACKGROUND: Inflammation is a double-edged sword in the pathophysiology of chronic diseases, such as type 2 diabetes mellitus (T2DM). The global rise in the prevalence of T2DM in one hand, and poor disease control with currently-available treatments on the other hand, along with an increased tendency towards the use of natural products make scientists seek herbal medicines for the management of diabetes and its complications by reducing C-reactive protein (CRP) as an inflammatory marker. PURPOSE: To systematically review the literature to identify the efficacy of various medicinal plants with antioxidative and anti-inflammatory properties considering their effect on CRP in animal models of T2DM. STUDY DESIGN: systematic review. METHODS: Electronic databases including PubMed, Scopus, Web of Science and Cochran Library were searched using the search terms "herbal medicine", "diabetes", "c-reactive protein", "antioxidants" till August 2021. The quality of evidence was assessed using the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE's) tool. The study protocol was registered in PROSPERO with an ID number CRD42020207190. A manual search to detect any articles not found in the databases was also made. The identified studies were then critically reviewed and relevant data were extracted and summarized. RESULTS: Among total of 9904 primarily-retrieved articles, twenty-three experimental studies were finally included. Our data indicated that numerous herbal medicines, compared to placebo or hypoglycemic medications, are effective in treatment of diabetes and its complications through decreasing CRP concentrations and oxidative stresses levels. Medicinal plants including Psidium guajava L., Punica granatum L., Ginkgo biloba L., Punica granatum L., Dianthus superbusn L.. Moreover, Eichhornia crassipes (Mart.) Solms, Curcuma longa L., Azadirachta indica A. Juss., Morus alba L., and Ficus racemosa L. demonstrated potential neuroprotective effects in animal models of diabetes. CONCLUSION: Hypoglycemic medicinal plants discussed in this review seem to be promising regulators of CRP, and oxidative stress. Thus, these plants are suitable candidates for management of diabetes' complications. Nevertheless, further high-quality in vivo studies and clinical trials are required to confirm these effects.

The effects of medicinal herbs on gut microbiota and metabolic factors in obesity models: A systematic review.

BACKGROUND AND AIMS: This systematic review of animal studies aimed to identify anti-obesity medicinal herbs with prebiotic properties, and investigate their effects on gut microbiota and metabolic disorders. METHODS: To obtain the relevant publications, four electronic databases were systematically searched up to June 2019. RESULTS: Out of 1949 publications, 20 articles met the inclusion criteria in this study. Apart from body weight, some cases (n = 11) had reported the effects of medicinal herbs on metabolic parameters, including lipid profile (n = 7) and glycemic status (n = 4). CONCLUSION: Although some medicinal herbs could be effective in modulating metabolic status and body weight, through making changes in the gut flora, further studies are needed to confirm the efficacy of such herbs in clinical trials.

Association of amino acid metabolites with osteoporosis, a metabolomic approach: Bushehr elderly health program.

INTRODUCTION AND OBJECTIVES: Amino acids are the most frequently reported metabolites associated with low bone mineral density (BMD) in metabolomics studies. We aimed to evaluate the association between amino acid metabolic profile and bone indices in the elderly population. METHODS: 400 individuals were randomly selected from 2384 elderly men and women over 60 years participating in the second stage of the Bushehr elderly health (BEH) program, a population-based prospective cohort study that is being conducted in Bushehr, a southern province of Iran. Frozen plasma samples were used to measure 29 amino acid and derivatives metabolites using the UPLC-MS/MS-based targeted metabolomics platform. We conducted Elastic net regression analysis to detect the metabolites associated with BMD of different sites and lumbar spine trabecular bone score, and also to examine the ability of the measured metabolites to differentiate osteoporosis. RESULTS: We adjusted the analysis for possible confounders (age, BMI, diabetes, smoking, physical activity, vitamin D level, and sex). Valine, leucine, isoleucine, and alanine in women and tryptophan in men were the most important amino acids inversely associated with osteoporosis (OR range from 0.77 to 0.89). Sarcosine, followed by tyrosine, asparagine, alpha aminobutyric acid, and ADMA in women and glutamine in men and when both women and men were considered together were the most discriminating amino acids detected in individuals with osteoporosis (OR range from 1.15 to 1.31). CONCLUSION: We found several amino acid metabolites associated with possible bone status in elderly individuals. Further studies are required to evaluate the utility of these metabolites as clinical biomarkers for osteoporosis prediction and their effect on bone health as dietary supplements.

Molecular Docking as a Therapeutic Approach for Targeting Cancer Stem Cell Metabolic Processes.

Cancer stem cells (CSCs) are subpopulation of cells which have been demonstrated in a variety of cancer models and involved in cancer initiation, progression, and development. Indeed, CSCs which seem to form a small percentage of tumor cells, display resembling characteristics to natural stem cells such as self-renewal, survival, differentiation, proliferation, and quiescence. Moreover, they have some characteristics that eventually can demonstrate the heterogeneity of cancer cells and tumor progression. On the other hand, another aspect of CSCs that has been recognized as a central concern facing cancer patients is resistance to mainstays of cancer treatment such as chemotherapy and radiation. Owing to these details and the stated stemness capabilities, these immature progenitors of cancerous cells can constantly persist after different therapies and cause tumor regrowth or metastasis. Further, in both normal development and malignancy, cellular metabolism and stemness are intricately linked and CSCs dominant metabolic phenotype changes across tumor entities, patients, and tumor subclones. Hence, CSCs can be determined as one of the factors that correlate to the failure of common therapeutic approaches in cancer treatment. In this context, researchers are searching out new alternative or complementary therapies such as targeted methods to fight against cancer. Molecular docking is one of the computational modeling methods that has a new promise in cancer cell targeting through drug designing and discovering programs. In a simple definition, molecular docking methods are used to determine the metabolic interaction between two molecules and find the best orientation of a ligand to its molecular target with minimal free energy in the formation of a stable complex. As a comprehensive approach, this computational drug design method can be thought more cost-effective and time-saving compare to other conventional methods in cancer treatment. In addition, increasing productivity and quality in pharmaceutical research can be another advantage of this molecular modeling method. Therefore, in recent years, it can be concluded that molecular docking can be considered as one of the novel strategies at the forefront of the cancer battle via targeting cancer stem cell metabolic processes.

The Probable Protective Effect of Photobiomodulation on the Inflammation of the Airway and Lung in COVID-19 Treatment: A Preclinical and Clinical Meta-Analysis.

Preliminary studies also show that many of the fatalities of COVID-19 are due to over-activity of the immune system, and photobiomodulation (PBM) therapy mainly accelerates wound healing and reduces pain and inflammation. Therefore, this systematic review and meta-analysis was conducted to evaluate the probable effect of the PBM therapy on the lung inflammation or ARDS and accelerate the regeneration of the damaged tissue. We systematically searched major indexing databases, including PubMed/Medline, ISI web of science (WOS), Scopus, Embase, and Cochrane central, using standard terms without any language, study region, or type restrictions. Of the 438 studies found through initial searches, 13 met the inclusion criteria. After applying the exclusion criteria, the main properties of 13 articles on 384 animals included in this meta-analysis with a wide range of species include rat (n = 10) and rabbit (n = 3). The analysis revealed that PBM therapy reduced TNFα (SMD:-3.75, 95% CI: -4.49, -3.02, P < 0.00001, I2 = 10%), IL-1ß (SMD:-4.65, 95% CI: -6.15, -3.16, P < 0.00001, I2 = 62%), and IL-6 (SMD:-4.20, 95% CI: -6.42, -1.97, P = 0.0002, I2 = 88%) significantly compared with the model controls. Hence, PBM therapy increased IL-10 significantly compared with the model controls (SMD:-4.65, 95% CI: -6.15, -3.16, P < 0.00001, I2 = 62%). PBM therapy also reduced MPO activity (SMD:-2.13, 95% CI: -3.38, -0.87, P = 0.0009, I2 = 64%) and vascular permeability (SMD:-2.59, 95% CI: -4.40, -0.77, P = 0.0052, I2 = 71%) in the lung using the Evans blue extravasation technique significantly compared with the model controls. This systematic review and meta-analysis revealed that the PBM therapy does utilize beneficial anti-inflammatory effect, modulation of the immune system, lung permeability, or bronchoalveolar lavage on lung damage in both animal models and clinical studies. However, animal model and clinical studies appear limited considering the quality of the included evidences; therefore, large clinical trials are still required.

Factors associated with TBS worse than BMD in non-osteoporotic elderly population: Bushehr elderly health program.

BACKGROUND: Bone mineral density (BMD) and trabecular bone score (TBS) are moderately correlated. TBS is sometimes used as an adjuvant to BMD in the fracture risk assessment. Some individuals with normal BMD or osteopenia, have more degraded TBS. We aimed to identify factors associated with TBS worse than BMD in the non-osteoporotic elderly population. METHODS: The study subjects were selected from 2384 women and men aged ≥60 years participating in the second stage of the Bushehr Elderly Health program, a population-based prospective cohort study in Iran. The BMDs of different sites and the lumbar spine texture were measured using dual-energy X-ray absorptiometry and the TBS algorithm, respectively. Subjects were categorized based on their BMD and TBS status. Logistic regression was performed to identify the factors associated with "TBS worse than BMD" in non-osteoporotic individuals. RESULTS: Of 1335 participants included in the study, 112 of 457 women, and 54 of 878 men had worse TBS than BMD. In multivariable analysis, TBS worse than BMD in women was statistically significantly associated with years since menopause (OR: 1.04 (1.00-1.07)) and waist circumference (OR: 1.09 (1.05-1.14)). However, in men, the condition was statistically significantly associated with waist circumference (OR: 1.10 (1.03-1.17)), current smoking (OR: 2.54 (1.10-5.84)), and HDL-C (OR: 1.03 (1.00-1.06)). CONCLUSION: The results of the study show that higher waist circumference is associated with more degraded TBS than BMD in both men and women. Years passed since menopause and current smoking, respectively in women and men, were associated with more degraded TBS. Considering TBS values in older individuals with higher waist circumference, or a history of smoking despite normal BMDs might help more accurate assessment of bone health. However, further studies are required to confirm the benefit.

Mass spectrometry with derivatization method for concurrent measurement of amino acids and acylcarnitines in plasma of diabetic type 2 patients with diabetic nephropathy.

BACKGROUND: Amino acids (AAs) and acylcarnitines play a key role in metabolic disease and can be used as biomarkers of various diseases such as malignancies, type 2 diabetes (T2D), insulin resistance, and cardiovascular diseases, therefore, designing an accurate and simple laboratory method that simultaneously measure both groups of substances, could improve the process of analytes quantification. In this research, a flow injection tandem mass spectrometry (FI-MS/MS) method for simultaneous measurement of AAs and acylcarnitines in addition to results of validation is explained. METHODS: Samples were mixed with internal standards and after derivatization (with butanolic-HCL), AAs, and acylcarnitines were quantified by tandem mass spectrometry (SCIEX API 3200). Analytical performance studies were designed based on the Clinical and Laboratory Standards Institute (CLSI) guidelines including precision, accuracy, linearity, and limit of detection-quantification (LOD-LOQ) experiments. Samples from patients with T2D in different stages of kidney disease were also analyzed to ensure the clinical usage of the method. RESULTS: Performance evaluation of the method demonstrated adequate results. The mean of estimated inter-assay precision (reported as a coefficient variation) for AAs and acylcarnitines were less than 8.7% and 12.3%, the estimated mean bias was below 8.8% and 10.2% respectively. LOD of analytes ranged between 0.6-10 µmol per liter (µmol/L) for AAs and 0.02-1 µmol/L for acylcarnitines. LOQ analytes showed a range of 2-25 µmol/L and 0.05-5 µmol/L for AAs and carnitine/acylcarnitines respectively. In diabetic patients sample analysis, a significant increase in acylcarnitines (C2, C4, C5DC, C6, C8, C10, C14) and citrulline with a significant decrease in valine were seen in patients with severely increased albuminuria. CONCLUSION: FI-MS/MS method with pre-injection derivatization with butanolic-HCL can be used for concurrent measurement of AAs and carnitine/acylcarnitines in a short time and it satisfies the analytical performance requirements. This method is applied for AAs and carnitine/acylcarnitines measurement in patient with T2DM and results show some of the acylcarnitines and AAs can be involved in diabetic nephropathy development. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-021-00786-3.

Neuroprotective Properties of Photobiomodulation in Retinal Regeneration in Rats: Perspectives From Interaction Levels.

Introduction: Photobiomodulation (PBM) is known as low-level laser (or light) therapy and is applied in different fields of medicine. However, it is required that its molecular and cellular mechanism be investigated. This study aims to assess the neuroprotective properties of PBM in the rat retina. Methods: GSE22818 was downloaded from Gene Expression Omnibus (GEO) and the regulation of the significant differentially expressed genes (DEGs) which are produced by light damage in the rat retina by the pretreatment of PBM application was assessed via network analysis and gene ontology enrichment. Results: The 78 produced DEGs by light-damage in the rat retina were protected via PBM pretreatment action. Among these determined DEGs, 53 individuals were included in the main connected component of the constructed protein-protein interaction (PPI) network. Ccl2, Icam1, Cxcl10, Timp1, and Fos were determined as hub nodes. Eight clusters including 26 regulated biochemical pathways by PBM pretreatment were identified. The critical DEGs based on the action maps were introduced. Conclusion: The finding indicates that PBM treatment protects rat retina against light damage via the prevention of Fos, Ccl2, Icam1, Cxcl10, and Myc dysregulation.

Development of a Novel Anti-Obesity Compound with Inhibiting Properties on the Lipid Accumulation in 3T3-L1 Adipocytes

Background: Obesity as a developing global challenge can be characterized by increase in adipocyte number and size arising from adipogenesis. Control of adipogenesis, as a potential strategy, can prevent and manage obesity. So far, the effectiveness of herbal medicine and active ingredients therapies for obesity and metabolic syndrome treatment has been investigated. In this study, a novel combination of berberine, catechin, and capsaicin was developed, and their effect on 3T3-L1 adipocytes was investigated. Mthods: The effect of active ingredient on the cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Adipocytes were treated with various concentrations of berberine (3 and 6.25 µM), catechin (6.25 and 12.5 µM), and capsaicin (6.25 and 12.5 µM) alone and in combination. Results: All active ingredients did not affect the cell viability by MTT assay at different concentrations. The dual and triple combinations of three active ingredients showed excellent potential as anti-obese without any toxicity. The inhibitory effect of berberine, catechin, and capsaicin on the differentiation of 3T3-L1 preadipocytes was found to be dose-dependent. These results indicate that catechin in both doses may have a stronger effect than the two other active ingredients on the intracellular lipid accumulation. Also, the triple combination of the aforementioned ingredients showed better responses than their dual combination. Conclusion: This work is the first report to simultaneously investigate these three active ingredients in a single, dual, and triple formats. The berberine, catechin, and capsaicin co-treatment inhibits the adipogenesis during the differentiation process. This compound can be a prospective therapy for obesity and relevant diseases such as dyslipidemia.

Role of Flt4 in Skin Protection against UVB Radiation: A System Biology Approach.

Background: Although the application of ultraviolet B (UVB) in phototherapy of human skin is a common therapeutic method, it is known as a risk factor for skin cancer. This study aims to assess the role of differentially expressed genes (DEGs) to find the critical one that is mainly responsible for skin protection against UVB radiation. Methods: The gene expression profiles of irradiated mice by UVB that issued skin protection against exposure are extracted from Gene Expression Omnibus (GEO) and analyzed by GEO2R. The significant DEGs are assessed via gene ontology (GO) analysis and the critical individuals are investigated via action mapping. Results: Thirty-eight significant DEGs that provide skin resistance against UVB irradiation were determined. Among the query DEGs, 26 individuals were related to 43 biological terms. Flt4, F3, Tspan6, Cblb, and Itgb6 were highlighted as the critical DEGs to promote skin protection against UVB irradiation. Conclusion: The finding indicates that Flt4 is the key DEG that is mainly responsible for protecting skin from UVB exposure.