Herbal-based therapeutics for diabetic patients with SARS-Cov-2 infection.

Human SARS Coronavirus-2 (SARS-CoV-2) has infected more than 170 million people worldwide, being responsible for about 3.5 million deaths so far. Despite ongoing investigations, there is still more to understand the mechanism of COVID-19 infection completely. However, it has been evidenced that SARS-CoV-2 can cause Coronavirus disease (COVID-19) notably in diabetic people. Approximately 35% of the patients who died of this disease had diabetes. A growing number of studies have evidenced that hyperglycemia is a significant risk factor for severe SARS-CoV-2 infection and plays a key role in COVID-19 mortality and diabetes comorbidity. The uncontrolled hyperglycemia can produce low-grade inflammation and impaired immunity-mediated cytokine storm that fail multiple organs and sudden death in diabetic patients with SARS-CoV-2 infection. More importantly, SARS-CoV-2 infection and interaction with ACE2 receptors also contribute to pancreatic and metabolic impairment. Thus, using of diabetes medications has been suggested to be beneficial in the better management of diabetic COVID-19 patients. Herbal treatments, as safe and affordable therapeutic agents, have recently attracted a lot of attention in this field. Accordingly, in this review, we intend to have a deep look into the molecular mechanisms of diabetic complications in SARS-CoV-2 infection and explore the therapeutic potentials of herbal medications and natural products in the management of diabetic COVID-19 patients based on recent studies and the existing clinical evidence.

Potential therapeutic options for COVID-19: an update on current evidence.

SARS-CoV-2, a novel coronavirus, is the agent responsible for the COVID-19 pandemic and is a major public health concern nowadays. The rapid and global spread of this coronavirus leads to an increase in hospitalizations and thousands of deaths in many countries. To date, great efforts have been made worldwide for the efficient management of this crisis, but there is still no effective and specific treatment for COVID-19. The primary therapies to treat the disease are antivirals, anti-inflammatories and respiratory therapy. In addition, antibody therapies currently have been a many active and essential part of SARS-CoV-2 infection treatment. Ongoing trials are proposed different therapeutic options including various drugs, convalescent plasma therapy, monoclonal antibodies, immunoglobulin therapy, and cell therapy. The present study summarized current evidence of these therapeutic approaches to assess their efficacy and safety for COVID-19 treatment. We tried to provide comprehensive information about the available potential therapeutic approaches against COVID-19 to support researchers and physicians in any current and future progress in treating COVID-19 patients.

Performance of capecitabine in novel combination therapies in colorectal cancer.

Colorectal cancer is one of the most common cancers throughout the world, and no definitive cure has ever been found. Perhaps a new insight into the effectiveness of chemotherapy drugs could help better treat patients. Targeted therapies have significantly improved the median overall survival of colorectal cancer patients. One of the standard chemotherapy regimens used for colorectal cancer is capecitabine, which is important in monotherapy and combination therapies. Capecitabine, with other chemotherapeutic agents (irinotecan, oxaliplatin, perifosine, 17-allylamino-17-demethoxygeldanamycin, aspirin, celecoxib, statins, quinacrine, inositol hexaphosphate and inositol, cystine/theanine, curcumin, and isorhamnetin), and biological ones (antibodies) plays an important role in the inhibition of some signaling pathways, increasing survival, reducing tumor growth and side effects of capecitabine. However, some drugs, such as proton pump inhibitors, are negatively related to capecitabine; therefore, the purpose of this work is to review and discuss the performance of capecitabine combination therapies in colorectal cancer.

The effects of nanocurcumin supplementation on inflammation in hemodialysis patients: A randomized controlled trial.

INTRODUCTION: Serum levels of several pro-inflammatory cytokines are higher in hemodialysis patients compared to healthy people. Curcumin has been shown to be able to decrease cytokines levels in nonuremic subjects. Our goal was to evaluate the effect of nanocurcumin administration on cytokines levels in hemodialysis patients. METHODS: The study was performed over a 3 months period on 54 hemodialysis patients who had been randomized to receive either nanocurcumin or placebo. Serum levels and gene expressions of tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) were evaluated using enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR). FINDINGS: Serum levels of IL-6 and TNF-α were similar in the two groups at baseline but were lower after 12 weeks of treatment with nanocurcumin compared to placebo (P = 0.024 for IL-6 and 0.02 for TNF). In the group given nanocurcumin, serum levels of both cytokines decreased substantially (P < 0.001 for each), whereas they were unchanged in the group given placebo. Gene expression for each cytokine in peripheral blood mononuclear cells (PBMCs) was reduced at 12 weeks vs. baseline in the group given nanocurcumin, and changes in gene expression correlated with changes in serum level for each of the two cytokines. DISCUSSION: The results indicate that nanocurcumin supplementation reduces both serum levels and gene expression of IL-6 and TNF-α in hemodialysis patients. The feasibility and potential clinical benefits of nanocurcumin treatment to reduce inflammation in hemodialysis patients warrant further study.

The Effects of Nano-curcumin Supplementation on Serum Level of hs-CRP, Adhesion Molecules, and Lipid Profiles in Hemodialysis Patients, A Randomized Controlled Clinical Trial.

INTRODUCTION: Hemodialysis (HD) patients are considered as a high-risk population for cardiovascular disease, within which morbidity and mortality have been determined to be associated with dyslipidemia, pro-inflammatory cytokines, increased levels of C-reactive protein (CRP), and adhesion molecules (ICAM-1, VCAM-1). Different markers have been investigated to detect inflammation in hemodialysis patients, as well as the prognostic values of these markers. METHODS: The present study aimed to investigate the effect of nano-curcumin (120 mg) over 12 weeks on hs-CRP levels, adhesion molecules (ICAM-1, VCAM-1), and serum lipid profiles on hemodialysis patients in a randomized controlled clinical trial. RESULTS: The results revealed that the mean serum hs-CRP level in the nano-curcumin group exhibited a decrease by the end of the study, when compared to mean serum hs-CRP level in the placebo group. However, this between-group trend was not found to be statistically significant (P > .05). Nevertheless, a significant difference was determined between the values in the group receiving nano-curcumin, in comparison with the placebo group, at the end of the study (P < .001). Based on the attained results, mean serum levels of VCAM-1 in the nano-curcumin group were significantly reduced at the end of the study, compared with the placebo group (P < .001). Furthermore, the between-group changes comparison showed significant reductions in serum levels of ICAM- 1 in patients treated with nano-curcumin at the end of the study (P < .05). Additionally, though decreases in mean triglycerides, total cholesterol, LDL-C were noted, there were no statistically significant between-group differences (P > .05). Moreover, between-group changes comparison of HDL-C levels and fasting blood sugar did not show any significant changes. CONCLUSION: The current study indicates that nano-curcumin may show beneficial effects in lowering inflammation and hs-CRP levels, as well as adhesion molecules (ICAM-1, VCAM-1), in hemodialysis patients. However, the evidence is still insufficient.

A randomized controlled study of dose-finding, efficacy, and safety of mulberry leaves on glycemic profiles in obese persons with borderline diabetes.

OBJECTIVES: Mulberry (Morus alba L.) leaves have been used in traditional medicine for treating hyperglycemia. However, there remains difficulties in the implementation of mulberry leaves in evidence-based practice. The aims of this study were to examine the optimal dose of 1-deoxynojirimycin (DNJ) in mulberry leaves and to determine the efficacy and safety of mulberry leaves in glycemic control in obese persons with borderline diabetes. DESIGN: First, healthy adults were recruited into the dose-finding study and randomly allocated to ingest sucrose solution concurrently with mulberry leaf powder at weights equivalent to 0 (control), 6, 12, and 18 mg of DNJ. Postprandial glucose and undesirable effects were evaluated. Second, obese persons with borderline diabetes were randomly assigned into the mulberry-leaves treatment group (12 mg of mulberry DNJ three times daily) and the control group in the 12-week prospective study. Blood glucose and insulin as well as adverse effects were determined. RESULTS: Twelve mg of mulberry DNJ was the minimum effective dose attenuating postprandial hyperglycemia. Mulberry leaves decreased fasting plasma glucose (FPG) by 3.86 ± 5.99 mg/dL (p = 0.002) and glycated hemoglobin (HbA1c) by 0.11 ± 0.22 % (p = 0.011) when compared with the baseline levels. Improvement in glucose tolerance was not observed. Furthermore, mulberry leaves tended to ameliorate insulin resistance (p = 0.057). Adverse events of mulberry leaves commonly found in this study were gastrointestinal symptoms including bloating, flatulence, and loose stools. CONCLUSION: Mulberry leaves possessed favorable effects on glycemic profiles without serious side effects.

Curcumin modulates the angiogenic potential of human endothelial cells via FAK/P-38 MAPK signaling pathway.

Many phyto-compounds are found to have anti-angiogenesis property. Curcumin, a natural polyphenol, has been used as medicinal plant for years with different biological activities. Here, we investigated the effect of curcumin on angiogenesis potential of human endothelial cells. Human Umbilical Vein Endothelial Cells (HUVECs) were treated with different concentration of curcumin over a period of 72 h. Cell survival rate was measured by MTT assay. Cell migration and tubulogenesis were studied by scratch and tubulogenesis assays. The expression level of VEGF was monitored by RT-PCR. We also monitored the phosphorylation of FAK and P-38 MAPK by western blotting. Compared to control group, curcumin decreased HUVECs survival rate after 72 h. We found that the migration of HUVECs was decreased after curcumin treatment compared to the control (p < 0.0001). Cell alignment and tubulogenesis activity were found to be inhibited compared to cells from the VEGF group (p < 0.05). The expression level of VEGF was increased in curcumin treated cells at first 24 h time period. Based on data from the current experiment, the protein level of p-FAK/FAK ratio was increased coincided with a decrease in p-P38/P38 ratio treatment with curcumin (p < 0.0001). These data demonstrated that curcumin inhibited HUVECs angiogenesis potential by modulation of FAK/P-38 MAPK signaling pathway.

Study of the Binding Interaction between Wortmannin and Calf Thymus DNA: Multispectroscopic and Molecular Docking Studies.

INTRODUCTION: Wortmannin (WTN) is a steroid metabolite that inhibits phosphatidylinositol 3-kinase and other signaling pathways. Structurally, the WTN consists of a cyclopentanophenanthrene-like structure with several oxygen-rich moieties which have the potential to interact with deoxyribonucleic acid (DNA) molecules. METHODS: We aim to evaluate the WTN and calf thymus DNA (ct-DNA) interaction with molecular docking using the AutoDock 4.2 software. UV and fluorescence spectroscopy and viscosity techniques were performed to confirm the in silico analysis. RESULTS: Molecular docking showed that the WTN interacted with ct-DNA via hydrogen bonds at guanine-rich sequences. The number of hydrogen bonds between the WTN and DNA was 1-2 bonds (average 1.2) per WTN molecule. The in silico binding constant was 2 × 103 M-1. UV spectroscopy showed that the WTN induced a hyperchromic feature without wavelength shifting. The WTN and DNA interaction led to quenching of DNA-emitted fluorescence. The different concentrations of WTN had no effect on DNA viscosity. Taken together, our results demonstrated WTN interacts with DNA in the nonintercalating mode, which is considered as a new mechanism of action. CONCLUSION: These results suggest that the WTN may exert its biological effects, at least in part, via interaction with DNA.

Rescue effects of ginger extract on dose dependent radiation-induced histological and biochemical changes in the kidneys of male Wistar rats.

Radiation is an essential modality in the management of cancer therapy, but its acute and chronic side effects on the normal organs limit the helpfulness of radiotherapy. The deleterious effects of radiation begin with oxidative stress and inflammatory reaction to radiolytic hydrolysis and formation of free radicals. The aim of the current study was to investigate the effect of dose dependent whole body radiation exposure on histological and biochemical alterations in rat kidney. It was also planned to find out whether ginger extract mitigated the deleterious effects of different doses of radiation in rat kidney. Male Wistar rats were exposed to three doses (2, 4, and 8Gy) of γ- ray with or without a 10day pretreatment with ginger extract. After 10days of whole body γ- ray exposure, the results revealed proliferation of glomerular and tubular cells, fibrosis in glomerular and peritubular and a significant increase in 8-OHdG, CRP, cystatin C (in 8Gy), plasma urea and creatinine levels, as well as a significant decrease in total antioxidant capacity of radiation groups compared to those of the control group. Ginger extract administration once daily for 10 consecutive days before exposure to 2-4-8Gy radiotherapy, which ameliorated histological and biochemical alterations in kidneys of the rats entirely or partially compared to those in the ethanol group rats. These findings indicate that whole body exposure to radiation induces kidney damage through oxidative DNA damage and inflammatory reactions, and that these effects can be alleviated using ginger pretreatment as an antioxidant and anti-inflammatory agent.

Ginger extract mitigates ethanol-induced changes of alpha and beta - myosin heavy chain isoforms gene expression and oxidative stress in the heart of male wistar rats.

The association between ethanol consumption and heart abnormalities, such as chamber dilation, myocyte damage, ventricular hypertrophy, and hypertension is well known. However, underlying molecular mediators involved in ethanol-induced heart abnormalities remain elusive. The aim of this study was to investigate the effect of chronic ethanol exposure on alpha and beta - myosin heavy chain (MHC) isoforms gene expression transition and oxidative stress in rats' heart. It was also planned to find out whether ginger extract mitigated the abnormalities induced by ethanol in rats' heart. Male wistar rats were divided into three groups of eight animals as follows: Control, ethanol, and ginger extract treated ethanolic (GETE) groups. After six weeks of treatment, the results revealed a significant increase in the ß-MHC gene expression, 8- OHdG amount, and NADPH oxidase level. Furthermore, a significant decrease in the ratio of α-MHC/ß-MHC gene expression to the amount of paraoxonase enzyme in the ethanol group compared to the control group was found. The consumption of Ginger extract along with ethanol ameliorated the changes in MHC isoforms gene expression and reduced the elevated amount of 8-OHdG and NADPH oxidase. Moreover, compared to the consumption of ethanol alone, it increased the paraoxonase level significantly. These findings indicate that ethanol-induced heart abnormalities may in part be associated with MHC isoforms changes mediated by oxidative stress, and that these effects can be alleviated by using ginger extract as an antioxidant molecule.

Short-term buserelin administration induces apoptosis and morphological changes in adult rat testes.

PURPOSE: To investigate the effect of buserelin on gonadal structure and function in adult male rats. METHODS: Twenty-four adult Wistar male rats were divided into three groups: two treated groups and controls. The first and second treated groups received 300 (low dose) and 500 (high dose) µg/kg buserelin, respectively, and the control group received normal saline. All groups were treated subcutaneously for five days. RESULTS: The seminiferous tubular epithelial thickness was significant decreased in the treated groups compared with those in the control. There was a significant increase in apoptotic cell death in high dose treated group compared with low dose treated and control groups. No significant difference in serum testosterone level was observed after one month in the three groups. CONCLUSION: Buserelin induces apoptotic cell death and decreased diameter and epithelium thickness of seminiferous tubules in the adult rat testes.

Short-term buserelin administration induces apoptosis and morphological changes in adult rat testes

Abstract Purpose: To investigate the effect of buserelin on gonadal structure and function in adult male rats. Methods: Twenty-four adult Wistar male rats were divided into three groups: two treated groups and controls. The first and second treated groups received 300 (low dose) and 500 (high dose) µg/kg buserelin, respectively, and the control group received normal saline. All groups were treated subcutaneously for five days. Results: The seminiferous tubular epithelial thickness was significant decreased in the treated groups compared with those in the control. There was a significant increase in apoptotic cell death in high dose treated group compared with low dose treated and control groups. No significant difference in serum testosterone level was observed after one month in the three groups. Conclusion: Buserelin induces apoptotic cell death and decreased diameter and epithelium thickness of seminiferous tubules in the adult rat testes.

Ginger extract protects rat's kidneys against oxidative damage after chronic ethanol administration.

Chronic alcohol ingestion is associated with pronounced detrimental effects on the renal system. In the current study, the protective effect of ginger extract on ethanol-induced damage was evaluated through determining 8-OHdG, cystatin C, glomerular filtration rate, and pathological changes such as cell proliferation and fibrosis in rats' kidneys. Male wistar rats were randomly divided into three groups and were treated as follows: (1) control, (2) ethanol and (3) ginger extract treated ethanolic (GETE) groups. After a six weeks period of treatment, the results revealed proliferation of glomerular and tubular cells, fibrosis in glomerular and peritubular and a significant rise in the level of 8-OHdG, cystatin C, plasma urea and creatinine. Moreover, compared to the control group, the ethanol group showed a significant decrease in the urine creatinine and creatinine clearance. In addition, significant amelioration of changes in the structure of kidneys, along with restoration of the biochemical alterations were found in the ginger extract treated ethanolic group, compared to the ethanol group. These findings indicate that ethanol induces kidneys abnormality by oxidative DNA damage and oxidative stress, and that these effects can be alleviated using ginger as an antioxidant and anti-inflammatory agent.

Structure-toxicity relationships of thiono and seleno phosphoramidate compounds: new type of acetylcholinesterase inhibitors.

Novel thiono and seleno phosphoramidate compounds with the general formula (X)(Y)P(C(6)H(5))(2); (X = NMe(2) & Y = S, 1a; X = NEt(2) & Y = S, 2a; X = NMe(CH(2)Ph) & Y = S, 3a; X = NH(CH(2)Ph) & Y = S, 4a; X = NEt(CH(2)Ph) & Y = S, 5a; X = N(C(Me)(3)) (CH(2)Ph) & Y = S, 6a; X = N(CH(2)Ph)(2) & Y = S, 7a; X = NMe(2) & Y = Se, 1b; X = NEt(2) & Y = Se, 2b; X = NMe(CH(2)Ph) & Y = Se, 3b; X = NH (CH(2)Ph) & Y = Se, 4b; X = NEt(CH(2)Ph) & Y = Se, 5b; X = N(C(Me)(3))(CH(2)Ph) & Y = Se, 6b and X = N(CH(2)Ph)(2) & Y = Se, 7b) were prepared and characterized by (1)H, (31)P and( 13)C NMR and IR spectroscopy and elemental analysis. (31)P chemical shift of thiono and seleno derivatives didn't show significant different because of their little difference in electronegativity sulfur and selenium. Hydrophobic parameter of compounds was determined by measurement of octanol-water partition coefficient by shake-flask technique. Determination of human erythrocyte acetylcholinesterase (hAChE) activity was carried out according to the Ellman's modified kinetic method. IC(50 )values of the selected thiono and seleno compounds varied from 3.4 to 0.11 and 9.9 to 5.1 mM, respectively. The seleno compounds show lower affinities for hAChE relative to the thino compounds. These results demonstrate that hydrophobic and electronic factors of the organophosphorus compounds play a key role on the inhibitory potency.