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- Morin hydrate downregulates inflammation‐mediated nitric oxide
overproduction and potentiates antioxidant mechanism against anticancer drug doxorubicin oxidative hepatorenal toxicity in rats Abstract: Objective: Doxorubicin (DOX) is a frontline antineoplastic drug that kills cancer cells through genotoxic mechanism; however, it induces organ toxicities. This study assayed whether morin hydrate (MOH) could abrogate DOX hepatorenal toxicity in rats.
Materials and Methods: There were 4 groups of rats: Control, MOH, DOX and MOH + DOX. Rats were administered MOH (orally, 100 mg/kg bw) for 7 consecutive days, while DOX was injected (40 mg/kg, ip) on the 5th day only. Hepatorenal function markers, and glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) activities were estimated in both organs. Hepatorenal glutathione (GSH), malondialdehyde (MDA), and nitric oxide (NO) levels were estimated with histopathology.
Results: DOX significantly (p<0.05) reduced antioxidant enzyme activities and GSH level, while NO and MDA levels increased (p<0.05) compared to the control. DOX prominently altered hepatorenal indices and induced histopathological alterations. MOH abrogated the DOX hepatorenal toxicity and alleviated the histological lesions in the liver and kidney.
Conclusion: MOH restored the indices via antioxidant mechanism and downregulation of NO overproduction in rats.
- Potential therapeutic effects of baicalin and baicalein
Abstract: Objective: Baicalin and baicalein are natural flavonoids reported for the first time from Scutellaria baicalensis Georgi. Recently, attention has been paid to these valuable flavonoids due to their promising effects. This paper aims to have a comprehensive review of their pharmacological effects.
Materials and Methods: An extensive search through scientific databases including Scopus, PubMed, and ISI Web of Science was established.
Results: According to literature, these compounds have been mainly effective in the treatment of neurological and neurodegenerative diseases, hepatic and cardiovascular disorders, metabolic syndrome, and cancers through anti-inflammatory and antioxidant pathways. Induction of apoptosis and autophagy, and inhibition of migration and metastasis are the main mechanisms for their cytotoxic and antitumor activities. Decreasing inflammation, reducing oxidative stress, regulating the metabolism of lipids, and decreasing fibrosis, apoptosis, and steatosis are their main hepatoprotective mechanisms. Inhibiting the development of cardiac fibrosis and reducing inflammation, oxidative stress, and apoptosis are also the mechanisms suggested for cardioprotective activities. Decreasing the accumulation of inflammatory mediators and improving cognitive function and depressive-like behaviours are the main mechanisms for neurological and neurodegenerative activities.
Conclusion: The findings suggest the therapeutic potential of baicalin and baicalein. However, complementary research in different in vitro and in vivo models to investigate their mechanisms of action as well as clinical trials to evaluate their efficacy and safety are suggested.
- Investigating the effect of Nigella sativa on the testicular function of
first-generation offspring of mice treated with titanium oxide nanoparticles Abstract: Objective: Nanoparticles include primary particles with at least one of their dimensions being less than 100 nm. The goal of this research was to determine the possible protective role of Nigella sativa (NS) against toxic effects mediated by titanium oxide nanoparticle (TNP).
Materials and Methods: 30 adult mice (10 males and 20 females) were used. After mating, the pregnant female mice were randomly divided into 4 study groups (n=5 mice in each group). From the 13th day of gestation until delivery, the mice were given TNP and NS. After delivery, 10 newborn male mice were selected from each group and kept under standard conditions until puberty according to the previous grouping (4 groups). The epididymis of each mouse was removed and the sperm was collected for the evaluation of in vitro fertilization and testis for histopathology and spermatogenesis of in vitro fertilization of first-generation mice.
Results: No significant difference was observed between the NS group and the control group (p>0.05). In the TNP, a degree of epithelial lysis and a significant decrease in sperm motility was observed (p<0.05) compared with the control group. In the TNP and NS group, NS had an ameliorating effect on TNP-induced testicular germ cell damage (p<0.05).
Conclusion: In the present study, it was found that NS had no destructive effect on the germinal epithelium. However, NS had an ameliorating effect on TNP-induced testicular germ cell damage in mice.
- In vivo and in vitro effects of crocetin and its amide derivative on
acrylamide-induced neurotoxicity Abstract: Objective: Acrylamide (ACR) is a neurotoxic agent whose damage could be attenuated by antioxidants administration. Crocetin is a saffron-derived antioxidant that has neuroprotective effects. This study evaluates the protective effects of trans-sodium crocetinate (TSC) and its water-soluble derivative, Bis-N-(N-methylpyprazinyl) crocetinate (BMPC) against ACR neurotoxicity.
Materials and Methods: PC12 cells were treated with TSC and BMPC (1.95, 3.9, 7.81, 15.62, 31.25, 62.5, 125, 250, 500, and 1000 μM) for 24 hr. ACR was then added at a concentration of 6.5 mM (IC50), and cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. In the in vivo study, male Wistar rats were treated with ACR (50 mg/kg, intraperitoneal (i.p.)) for 11 days alone or in combination with TSC and BMPC (2.5, 5, and 10 mg/kg, i.p.) or vitamin E (200 IU/kg, i.p.). Motor impairments were then evaluated. The cerebral cortex of sacrificed rats was taken for the malondialdehyde (MDA) and glutathione (GSH) levels measurement.
Results: In vitro studies showed that TSC at a concentration of 7.81 μM and BMPC at concentrations of 3.9, 7.81, and 15.62 μM exhibited the lowest toxicity in acrylamide administration. In the in vivo study, pretreatment with 2.5, 5, and 10 mg/kg of TSC ameliorated behavioral impairments, but BMPC could not attenuate them. GSH and MDA were improved by 2.5, 5, and 10 mg/kg TSC and 2.5 mg/kg BMPC.
Conclusion: TSC and BMPC administration improved behavioral index and oxidative stress injuries in Wistar rats exposed to ACR through MDA reduction and GSH content enhancement in the cerebral cortex.
- Effect of misoprostol with and without evening primrose (Oenothera
biennis) on induction of missed abortion Abstract: Objective: To determine whether addition of evening primrose to a misoprostol-based abortion regimen can increase the success of abortion.
Materials and Methods: In this randomized clinical trial., 148 women referring to Niknafas Hospital in Rafsanajn with diagnosis of missed abortion were randomly allocated into two 74-subject groups. The intervention group used 2000 mg vaginal evening primrose capsules the night before the hospitalization, while the control group did not receive any medication. Both groups received an initial dose of 800 μg of vaginal misoprostol after admission and the next dose was given three hours later if necessary.
Results: The two groups had significant differences in terms of full abortion, consistency and dilatation of cervix, duration between the first dose of misoprostol until the ejection of fetus, the misoprostol dose administered, and the level of vaginal bleeding during the hospitalization. They had no significant differences regarding curettage, duration of hospitalization, or side effects. The mean pain score had no significant difference between the two groups, though the score was lower in the intervention group (p>0.05).
Conclusion: Administration of vaginal evening primrose before vaginal misoprostol was found to be more effective compared to misoprostol alone in missed abortion.
- Antidepressant effects of a Persian herbal formula on mice with chronic
unpredictable mild stress Abstract: Objective: Depression is a serious mental disorder. Despite numerous medications, there are still limitations in depression treatment. So, herbal medicine has been considered an alternative therapy. This survey evaluated the effects of a Persian herbal formula on mice with chronic unpredictable mild stress (CUMS).
Materials and Methods: A combination of Aloysia triphylla citrodora, Citrus aurantium, Echium amoneum, Lavandula angustifolia, Melissa officinalis, Salix aegyptiaca, Valeriana officinalis, Viola odorata, and Cinnamomum zeylanicum was prepared. Except for the control group, animals were subjected to CUMS for 8 weeks in 5 groups (n=10): CUMS, vehicle (distilled water), herbal formula (0.23 ml/mouse), fluoxetine (20 mg/kg), and bupropion (15 mg/kg). All administrations were performed orally daily for the last 4 weeks. The depression and anxiety-like behaviors were assessed by sucrose preference (SPT), tail suspension (TST), forced swimming (FST), and elevated plus-maze (EPM) tests. Superoxidase-dismutase (SOD) activities in tissues, and serum levels of cortisol, alanine-aminotransferase (ALT), and creatinine were measured. Also, histopathological changes were evaluated.
Results: This formula significantly increased SPT (p<0.001) and decreased immobility time in FST and TST (p<0.01), but it was not effective on EPM vs. CUMS mice. The herbal formula did not change the serum level of creatinine or ALT, but insignificantly reduced cortisol vs. CUMS and vehicle groups. SOD activity increased in the brain vs. vehicle group (p<0.05). There were no changes in histological examination.
Conclusion: The herbal formula improved depression-like behaviors which are possibly related to its anti-oxidative effect on the brain. Also, it did not cause any negative changes in the biochemical and histopathological analysis.
- Protective potential effects of hydroalcoholic extract of Teucrium polium
L. (Lamiaceae) against paraquat-induced lung fibrosis: An experimental study in rats Abstract: Objective: Paraquat (PQ) is a highly toxic herbicide that causes pulmonary fibrosis (PF), and no specific antidote is available against it. Teucrium polium L. is a plant that exhibits antioxidant and anti-inflammatory activities. The present study evaluates the preventive and therapeutic effects of T. polium extract (TPE) against PQ-induced lung fibrosis in rats.
Materials and Methods: We divided rats into five groups of eight. Groups one and two received saline and PQ (20 mg/kg, i.p.), respectively. Groups three to five were treated with TPE (50, 100, and 200 mg/kg, by gavage) started one week before PQ administration and lasted three weeks after PQ administration.
Results: Our findings showed that PQ significantly increased lung malondialdehyde, nitric oxide, hydroxyproline, lung index, Ashcroft score, red blood cells accumulation, and inflammatory cell infiltration. Moreover, PQ decreased catalase and glutathione peroxidase activities and glutathione content. The results of hematoxylin-eosin and Masson's trichrome staining indicated that PQ destroyed lung parenchyma and developed PF (p<0.05 to p<0.001). Gavage with TPE significantly improved biochemical and histological abnormalities induced by PQ in rats (p<0.05 to p<0.001).
Conclusion: The current survey indicated that treatment with TPE could reduce and reverse PQ-induced PF, which may be due to the phenolic compounds present in TPE.
- Hepatoprotective effects of brown algae Sargassum boveanum on bile
duct-ligated cholestasis in rats are mediated by modulating NF-κB/TNF-α and Nrf2/HO-1 gene expression Abstract: Objective: The current study assessed hepatoprotective effects of Sargassum boveanum (S. boveanum) in cholestatic rats. To induce cholestasis, bile duct ligation (BDL) was utilized.
Materials and Methods: Five groups of Sprague-Dawley rats including Sham and four BDL groups were assigned to receive vehicle (BDL-V) or ethanolic extract of S. boveanum at 100 (BDL-SE 100), 200 (BDL-SE 200) and 500 (BDL-SE 500) mg/kg/day for seven days.
Results: BDL group receiving the vehicle (BDL-V) had substantially increased blood levels of alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, total, and indirect bilirubin in comparison to the sham group. S. boveanum significantly decreased these variables compared to the BDL-V group. Hepatic malondialdehyde and tumor necrosis factor-α (TNF-α) level, and nuclear factor kappa light chain enhancer of activated B cells (NF-κB) and TNF-α gene expression were higher in BDL-V rats compared to the sham group but these were reduced markedly in BDL groups receiving S. boveanum in comparison to the BDL-V group. BDL-V group had a significantly lower hepatic glutathione value, glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity and gene expression of SOD, GPx, Nrf2, HO-1 in comparison to the sham group. S. boveanum prevented the decrease of these variables. The histopathological assay showed marked bile ducts proliferation, portal inflammation, and hepatocellular damage in the BDL-V group and S. boveanum administration remarkably reduced hepatic injury. Gas chromatography-mass spectroscopy (GC-MS) analysis revealed that S. boveanum ethanolic extract contained 39 active compounds.
Conclusion: S. boveanum treatment significantly ameliorated cholestatic hepatic injury via anti-oxidative and anti-inflammatory effects.
- Silibinin effects on cognitive disorders: Hope or treatment'
Abstract: Objective: Almost all diseases of the nervous system are related to neuroinflammation, oxidative stress, neuronal death, glia activation, and increased pro-inflammatory cytokines. Cognitive disorders are one of the common complications of nervous system diseases. The role of some plant compounds in reducing or preventing cognitive disorders has been determined. Silibinin is a plant bioflavonoid and exhibits various effects on cognitive functions. This article discusses the different mechanisms of the effect of silibinin on cognitive disorders in experimental studies.
Materials and Methods: Databases, including ISI, , Google Scholar, Scopus, Medline and PubMed, were investigated from 2000 to 2021, using related keywords to find required articles.
Results: Silibinin can improve cognitive disorders by different pathways such as reducing neuroinflammation and oxidative stress, activation of reactive oxygen species- Brain-derived neurotrophic factor- Tropomyosin receptor kinase B (ROS–BDNF–TrkB) pathway in the hippocampus, an increase of dendritic spines in the brain, inhibition of hyperphosphorylation of tau protein and increasing the expression of insulin receptor (IR) and insulin-like growth factor receptor 1 (IGF-1R), inhibiting inflammatory responses and oxidative stress in the hippocampus and amygdala, and decrease of Homovanillic acid/Dopamine (HVA/DA) ratio and 3,4-Dihydroxyphenylacetic acid + Homovanillic acid/Dopamine (DOPAC+ HVA/DA) ratio in the prefrontal cortex and 5-hydroxyindoleacetic acid/5-hydroxytryptamine (5-HIAA/5-HT) ratio in the hippocampus.
Conclusion: These results suggest that silibinin can be considered a therapeutic agent for the symptom reduction of cognitive disorders, and it acts by affecting various mechanisms such as inflammation, programmed cell death, and oxidative stress.
- Effect of nano-micelle curcumin on hepatic enzymes: A new treatment
approach for non-alcoholic fatty liver disease (NAFLD) Abstract: Objective: Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation in hepatocytes with no consumption of alcohol. Recently, curcumin is a natural polyphenol found in turmeric has been examined for the treatment of NAFLD. This study aimed to assess the efficacy of 160 mg/day nano-micelle curcumin on the amelioration of NAFLD by measuring liver enzymes.
Materials and Methods: Patients with NAFLD were randomly divided into curcumin (intervention group n=33) and placebo (n=33) groups and at the end of the study, the data of 56 participants who completed the 2-month intervention were analyzed. Laboratory tests and questionnaires were used to gather information. Both groups received recommendations for lifestyle modification, and were advised to other necessary advices. Patients in the curcumin group received 160 mg/day of nano-micelle curcumin in two divided doses for 60 days. The 2 groups were followed up for two months and clinical and laboratory indices were compared.
Results: Our data showed a significant decrease in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the curcumin group (p<0.01) as well as a significant difference between the groups before and after the intervention in curcumin group (p<0.05). Interestingly, a meaningful decrease in AST serum level was observed in the intervention group (p<0.01).
Conclusion: Our study demonstrated that short-term supplementation with nano-micelle curcumin results in the reduction of AST and ALT and is beneficial for the treatment of NAFLD.
- Protective effects of hydro-alcoholic extract of Zataria multiflora on
Abstract: Objective: Liver is an important player in regulation of body homeostasis. Study investigated the effects of hydro-alcohol extract of Zataria multiflora (ZM) on oxidative damage, level of IL-6 and enzymes of liver in lipopolysaccharide (LPS)-treated rats.
Materials and Methods: The rats were distributed into 5 groups: 1) Control; 2) LPS; and 3-5) ZM-Extract (Ext) 50, ZM-Ext 100, and ZM-Ext 200. ZM-Ext groups received 50, 100 and 200 mg/kg of extract 30 min before LPS. Drugs were injected intraperitoneally. The entire period of this project was 17 days. In first three days, only extract was injected and then, ZM was injected along with LPS.
Results: LPS increased the level of ALT (Alanine aminotransferase), AST (Aspartate aminotransferase ), ALK-P (Alkaline Phosphatase), IL-6, malondialdehyde (MDA), and nitric oxide (NO) metabolites and lowered thiol, superoxide dismutase (SOD) and catalase (CAT) concentration. ZM extract not only reduced ALT, AST, ALK-P, IL-6, MDA, and NO metabolites concentrations but also increased thiol content, and SOD and CAT levels.
Conclusion: Extract of ZM prevented LPS-induced hepatotoxicity. This protective effect was associated with reduction in inflammation and oxidative stress.
- Effects of curcumin supplementation on insomnia and daytime sleepiness in
young women with premenstrual syndrome and dysmenorrhea: A randomized clinical trial Abstract: Objective: Premenstrual syndrome and primary dysmenorrhea are common gynecological complaints that are associated with psychological disorders. There is increasing evidence for the neuroprotective properties of curcumin, a polyphenolic natural product. This study aimed to assess the effects of curcumin on sleep complications in women with premenstrual syndrome and dysmenorrhea.
Materials and Methods: This triple-masked, placebo-controlled clinical trial comprised 124 patients with both premenstrual syndrome and dysmenorrhea. Participants were randomly assigned to curcumin (n=57) or control (n=60) groups. Each participant received one capsule containing either 500 mg of curcumin plus piperine or placebo, daily, from 7 days before until 3 days after menstruation for three consecutive menstrual cycles. Insomnia and sleepiness were assessed using standard questionnaires.
Results: Scores for insomnia and daytime sleepiness were directly correlated with the Premenstrual Syndrome Screening Tool (PSST) score (p<0.05), but not with the visual analogue scale (VAS) score at baseline (p>0.05). There was a non-significant reduction in insomnia and sleepiness scores in both curcumin and placebo groups after the study intervention. Whilst, improvement rate of insomnia status, daytime sleepiness severity, short sleep duration and difficult sleep initiation was not statistically significant between the curcumin and placebo groups.
Conclusion: Curcumin does not significantly affect sleep disorders in young women with premenstrual syndrome and dysmenorrhea.
- Nephroprotective effects of Datura stramonium leaves against methotrexate
nephrotoxicity via attenuation of oxidative stress-mediated inflammation and apoptosis in rats Abstract: Objective: Methotrexate (MTX) is a frontline antimetabolite anticancer drug which is used in different cancer treatments but its nephrotoxicity is a notable drawback that limits its clinical use. The present study was undertaken to examine whether Datura stramonium leaf extract (DSLE) could block MTX nephrotoxic side effect in rats.
Materials and Methods: Animals were divided randomly into Control, Ethanol extract, MTX, and Extract + MTX groups. DSLE (200 mg/kg bw) was orally administered for 21 days, while MTX was injected intraperitoneally (ip) on the 18th day. Serum levels of urea, creatinine and uric acid were determined. Kidney samples were used to determine glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) activities, and renal levels of malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and caspase-3.
Results: Injection of MTX resulted in considerable increases (p<0.05) in creatinine, urea, and uric acid levels as well as renal MDA, NO, IL-6, TNF-α and caspase-3 compared to the controls. SOD and GPx increased significantly, while GSH was significantly depleted. Interestingly, DSLE markedly reduced (p<0.05) levels of creatinine, urea, uric acid, TNF-α, NO, MDA and caspase-3, whereas renal GSH increased markedly compared to the MTX group.
Conclusion: DSLE has nephroprotective activity against MTX toxicity. However, further mechanistic studies are needed.
- Effects of Iranian herbal Zofa® syrup for the management of clinical
symptoms in patients with COVID-19: A randomized clinical trial Abstract: Objective: The objective of this study was to determine the role of Iranian herbal Zofa® syrup in improving the clinical symptoms of patients with COVID-19.Materials and Methods: This randomized clinical trial was conducted on 105 patients with COVID-19. Patients were randomly assigned to the intervention (n=35) group (received 10 ml of Zofa® syrup every 8 hours/seven days plus standard treatment) or the control (n=70) group (received only standard treatment). Assessments were performed before and after treatment.Results: The groups were comparable regarding age (p=0.980), gender (p=0.584), comorbidities (p=0.318), or drug history (p=0.771). There was no difference between patients' recovery status at the time of discharge (p=0.327) or two weeks post-discharge (p=0.165) in the intervention and control groups. No patient was hospitalized to the intensive care unit (ICU) for supplemental oxygen therapy and no patient died in the intervention group. However, in the control group, three (4.5%) patients were transferred to the ICU, and two (3.03%) patients died.Conclusion: Considering the better recovery status of the patients at the time of discharge and the absence of patient deaths in the intervention group, more additional studies are needed to confirm these findings and elucidate the role of Zofa® in COVID-19.
- Cytotoxicity of curcumin against CD44± prostate cancer cells: Roles
of miR-383 and miR-708 Abstract: Objective: Cancer stem cells (CSCs) remaining in the tumor tissues after applying treatments may cause recurrence or metastasis of prostate cancer (PC). Curcumin has the promising potential to target CSCs. Here, we aim to evaluate the cytotoxic effects of curcumin on the expression of miR-383-5p and miR-708-5p and their target genes in CD44+ CSCs and CD44- non-CSCs isolated from the PC3 prostate cancer cell line.
Materials and Methods: We used MTT assay to determine the optimal cytotoxic dose of curcumin on CD44± PC cells. Then, we assessed nuclear morphological changes using DAPi staining. We used Annexin V-FITC/PI to quantify apoptotic cell death. qRT-PCR was also used to detect miRNA and gene expression levels after curcumin treatment.
Results: Curcumin significantly enhanced the apoptosis in both CD44- and CD44+ PC cells in a dose-dependent manner (p < 0.05). The cytotoxicity of curcumin against CD44- cells (IC50 40.30±2.32 μM) was found to be greater than that against CD44+ cells (IC50 83.31±2.91 μM). Also, curcumin promoted miR-383-5p and miR-708-5p overexpression while downregulating their target genes LDHA, PRDX3, and RAP1B, LSD1, respectively.
Conclusion: Our findings indicate that curcumin, by promoting the expression of tumor suppressors, miR-383-5p and miR-708-5p, and inhibiting their target genes, induced its cytotoxicity against CD44± PC cells. We trust that curcumin could be established as a promising adjuvant therapy to current PC treatment options following more research in clinical settings.
- Falcaria vulgaris L. hydroalcoholic extract protects against harmful
effects of mercuric chloride on the rat kidney Abstract: Objective: Mercuric chloride (Merc; HgCl2) is toxic to humans and animals and contributes to environmental pollution, which usually results in nerve and systemic harm to different organs. Falcaria vulgaris (FV) is a medicinal plant rich in antioxidants. This research aimed to assess the FV hydroalcoholic extract effects on kidney toxicity induced by Merc.
Materials and Methods: Forty-eight male rats were divided into eight groups: the control group: received saline; the Merc group: received 0.5 ml/day of 0.5 ppm aqueous Merc; FV1, 2, and 3 groups: received 50, 100, 150 mg/kg FV, respectively; and Merc + FV1, 2, and 3 groups: received Merc and FV at three doses. The administration period was 14-days. Subsequently, kidneys and sera were cumulated from each group for the analysis. Samples were analyzed via hematoxylin-eosin staining and biochemical tests.
Results: The rats that received Merc displayed significant decrement in the kidney index, the diameter of renal corpuscles, total antioxidant capacity levels, superoxide dismutase activity (all, p<0.01), and 150 mg/kg FV mitigated these outcomes (all, p<0.05). Urea, creatinine, nitric oxide, and the level of apoptosis revealed a significant increment in the kidney of the rats that received Merc (all, p<0.01), and 150 mg/kg FV decreased these results. Furthermore, FV ameliorated histological changes induced by Merc (all, p<0.05).
Conclusion: The FV hydroalcoholic extract protects the kidneys against Merc-induced nephrotoxicity. Antioxidant and anti-apoptotic FV hydroalcoholic extract properties were involved in this healing effect.
- Comparison of the effect of mint extract and chamomile drops on the
gastric residual volume of traumatic patients under mechanical ventilation and nasogastric tube feeding in the intensive care unit: A triple -blind, randomized, crossover trial Abstract: Objective: Mint and chamomile can effectively reduce the gastric residual volume (GRV). This study aimed to determine the effect of mint extract and chamomile drops on the GRV of trauma patients under mechanical ventilation and nasogastric tube feeding in the intensive care unit.
Materials and Methods: This study was a triple-blinded randomized clinical trial with a 2×2 crossover design. Eighty patients were randomly divided to receive mint extract and chamomile drops. Five drops of mint extract and 11 drops of chamomile were gavaged every 6 hr. GRV was measured using a syringe-aspiration method before and 3 hr after each intervention. After a 24-hour washout period, the two groups changed places.
Results: In the first phase of the study, before the interventions, the GRV in the mint and chamomile groups was 14.60±7.89 and 13.79±7.12 ml, and after the interventions were 8.13±6.31 and 6.61±4.68 ml, respectively. In the study's second phase, before the interventions, the GRV in the mint and chamomile groups was 10.03±4.93 and 11.46±7.17 ml and after the interventions, GRV was 4.97±4.05 and 6.98±4.60 ml, respectively. The difference in the GRV before and after the intervention was not significantly different between the two groups. Both herbal drugs effectively reduced the GRV (p=0.382).
Conclusion: Mint extract and chamomile drops are similarly effective in reducing the GRV in trauma patients under mechanical ventilation and nasogastric tube (NGT) feeding in the intensive care unit.
- A promising impact of oral administration of noscapine against
imiquimod-induced psoriasis-like skin lesions Abstract: Objective: Psoriasis is a chronic inflammatory autoimmune disease. The effectiveness of noscapine has been employed as a helpful treatment for various disorders and subjected to recent theoretical breakthroughs.
Materials and Methods: Psoriasis-like lesions were induced by topical application of 5% imiquimod (IMQ) (10 mg/cm2 of skin) in male Balb/c mice and then medicated with a single oral dose of methotrexate (MET) as a positive control or daily oral treatment of noscapine (5, 15 and 45 mg/kg). In this way, skin inflammation intensity, psoriatic itchiness, psoriasis area severity index (PASI) score, ear length, thickness, and organ weight were daily measured. At the end of the study, histological and immunohistochemical and enzyme-linked immunosorbent assays (ELISA, for pro-/anti-inflammatory factors) were performed in each ear.
Results: IMQ caused psoriasis-like lesions. Noscapine markedly alleviated macroscopic parameters, namely ear thickness, ear length, skin inflammation, itching, and organ weight, as well as microscopic parameters including, pathology and Ki67 and p53, and tissue immunological mediators, such as tumour necrosis factor (TNF-α), interleukin (IL)-10, transforming growth factor (TGF-β), interferon-g (IFN-g), IL-6, IL-17, and IL-23p19 in the psoriatic skin in a concentration manner (p<0.05-<0.001).
Conclusion: Therefore, noscapine with good pharmacological properties has considerable effects on psoriasis inflammation.
- Efficacy of topical galbanum oil with dry cupping in hospitalized COVID-19
patients: A randomized open-label clinical trial Abstract: Objective: This study was designed to detect the therapeutic effects of galbanum oil plus dry cupping (a Persian medicine-based method) in hospitalized patients with coronavirus disease-2019 (COVID-19).Materials and Methods: In this randomized controlled trial, 60 hospitalized COVID-19 patients with positive polymerase chain reaction test (PCR), pulmonary involvement and blood oxygen saturation (SpO2) ≤93 mmHg, were randomly assigned into two groups to take the standard therapeutic regimen alone or alongside cupping and topical galbanum oil (Ferula gommosa oleo-gum resin) for 3-5 days. The SpO2 level, the severity of signs and symptoms of patients and laboratory parameters were compared between the two groups.Results: Fifty-eight patients were analyzed. The SpO2 level changed from 89.27±3.82 to 90.29±3.09 mmHg (p=0.038) in control group, while it increased from 88.74±3.45 to 94.23±2.1 mmHg (<0.001) in galbanum group with a significant difference between the groups (p<0.001). Fever, cough, dyspnea, and anorexia alleviated in the galbanum group more than the control (p=0.003, 0.001, 0.01, and 0.04, respectively). No adverse effects were reported due to galbanum oil and cupping therapy.Conclusion: Dry cupping with galbanum oil alongside the routine therapeutic regimen could be more effective than the routine therapeutic regimen alone for improving SpO2 level and alleviating fever, cough, and dyspnea in COVID-19 patients.
- Review of the antioxidant potential of flavonoids as a subgroup of
polyphenols and partial substitute for synthetic antioxidants Abstract: Objective: This review describes the antioxidant activity of flavonoids as a subgroup of polyphenols and a partial or entire substitute for synthetic antioxidants.
Materials and Methods: All relevant databases were searched using the terms “Phytochemical”, “Polyphenol”, and “Flavonoid”.
Results: The oxidative reaction caused by free radicals is a reason for food spoilage, which causes unpleasant odor, loss of taste, and damaged tissues. The common antioxidants employed in foods include butylated hydroxyanisole, butylated hydroxytoluene, propyl gallate, and tert-butyl hydroquinone. Despite their high efficiency and potency, synthetic antioxidants have adverse effects on the human body, such as causing mutation and carcinogenicity. A whole and a group of them known as polyphenols possess high antioxidant activity. These compounds are potential antioxidants due to their capabilities such as scavenging free radicals, donating hydrogen atoms, and chelating metal cations. The antioxidant mechanism of action of flavonoids is transferring hydrogen atom to free radicals. Accordingly, the more the flavonoid structure makes the hydrogen transfer faster and easier, the more the flavonoid’s antioxidant power will be. Therefore, the antioxidant activity of the flavonoids with hydroxyl groups in their structure is the highest among different flavonoids.
Conclusion: In addition to health promotion and some disease prevention effects, various in vitro investigations have indicated that flavonoids possess high antioxidant activity that is comparable with synthetic antioxidants. However, to be commercially available, these compounds should be extracted from a low-price source with a high-performance method.
- Hepatic regenerative response to long-term consumption of cinnamon-rich
diet in aged rats Abstract: Objective: The present study aimed to investigate the impact of cinnamon on liver regeneration in a rat model of partial hepatectomy (PH).
Materials and Methods: Thirty-two old male Sprague-Dawley rats (12 weeks old) were randomly divided into two equal groups (n=16). One group was fed with a standard diet (control) while the other group was fed with the same diet containing 1% cinnamon for 41 weeks. Then, all animals were subjected to the PH procedure and their livers were studied on postoperative days 2, 10 and 28. The liver contents of hepatic growth factor (HGF), insulin, malondialdehyde (MDA), nitric oxide metabolites (NOx), superoxide dismutase (SOD) and tumor necrosis factor-alpha (TNF-α) were evaluated. Also, the serum levels of liver function markers (alanine aminotransferase (ALT) and aspartate aminotransferase (AST), MDA, NOx and SOD activity were measured.
Results: The regenerated liver weight was significantly higher in cinnamon-treated animals than the controls on both day 10 and 28 post hepatectomy. The hepatic MDA levels in the cinnamon-treated animals were significantly lower than the control rats. Cinnamon led to a significant increase of SOD on day 2 after hepatectomy in serum and liver content. The basal level of HGF in the liver of cinnamon-consuming rats was significantly higher than in the control rats. Hepatic insulin level was significantly increased relative to baseline and control on day 2 in the cinnamon-consuming rats. Hepatic TNF-α levels dramatically decreased on postoperative days (POD) 2 relative to baseline in the control and cinnamon-treated rats.
Conclusion: Long-term cinnamon consumption enhanced liver regeneration outcomes in old rats.
- The antidepressant effect of combined extracts of Hypericum perforatum and
Echium amoenum supplementation in patients with depression symptoms: A randomized clinical trial Abstract: Objective: Echium amoenum and Hypericum perforatum dried flowers have been used for therapy of mental disorders in Iranian traditional medicine. In this study, we assessed the efficacy of the E. amoenum and H. perforatum extracts in patients with mild to moderate depression.
Materials and Methods: In an 8-week double-blind, parallel-group trial, 51 patients randomly consumed 20 mg of fluoxetine or 350 mg of herbal medicine twice daily. The Hamilton Rating Scale for Depression (HAM-D) was used to assess depression severity in patients at weeks 0, 4, and 8.
Results: According to the Hamilton score, there were no significant differences between the fluoxetine- and herbal medicine-treated groups after 4 and 8 weeks (p>0.05). Dry mouth was the only reported side effect which was significantly lower in the herbal group (p<0.05) in weeks 2 and 4.
Conclusion: E. amoenum and H. perforatum have anti-depressant properties similar to fluoxetine and they can be used to treat depression as an alternative to fluoxetine.
- Antioxidant and anti-atherosclerotic potential of Banana (Musa spp): A
review of biological mechanisms for prevention and protection against atherosclerosis Abstract: Objective: To review the antioxidant and anti-atherosclerotic potential of whole banana, banana flour, and its bioactive compounds.
Materials and Methods: A non-systematic review of the literature covering the past 20 years, using the following databases and searching bases: PUBMED/MEDLINE: https://www.ncbi.nlm.nih.gov/pubmed/; Google Scholar: https://scholar.google.com.br/; and “Literatura Latinoamericana em Ciências da Saúde”/Latin American Literature in Life Sciences [LILACS]: http://lilacs.bvsalud.org/, was done. Studies with incomplete methodology and design were excluded.
Results: Bananas from different species are a good source of carbohydrates, dietary fiber, proteins, polyunsaturated fatty acids, potassium, carotenoids, flavonoids, vitamin C and E, phytosterols, gallocatechin, catechin, and other polyphenols. Some of these compounds play trigger important biological roles as antioxidants or anti-atherosclerotic and cardiovascular protective substances. This review summarizes and explains thirteen protective biological mechanisms of banana bioactive compounds and banana products.
Conclusion: Including banana and its products in dietary menus, in food products and nutraceuticals should improve cardiovascular health of the populations.
- Herbal medicines in the treatment of children and adolescents with
attention-deficit/hyperactivity disorder (ADHD): An updated systematic review of clinical trials Abstract: Objective: This study was performed to provide an updated systematic review of herbal medicines and phytochemicals used for treatment of the pediatric patients with attention-deficit/hyperactivity disorder (ADHD).
Materials and Methods: International electronic databases, including Scopus, PubMed, ScienceDirect, and Google Scholar were investigated from 1st January 2000 to late October 2021. Interventional studies published in English language, including randomized controlled trials (RCTs) or open-label clinical studies, which evaluated the effect of herbal medicines and phytochemicals on pediatric ADHD were included in this review.
Results: Fifteen studies met the inclusion criteria. Several pieces of evidence support the efficacy of Ginkgo biloba L. and Pycnogenol; mainly inconclusive evidence could be found for Valeriana officinalis L., Melissa officinalis L., and ginseng. The results showed that while Hypericum perforatum L. was ineffective for ADHD, Passiflora incarnata L., Crocus sativus L, and Prunus dulcis (Mill.) D.A.Webb had similar efficacy compared to methylphenidate (MPH).
Conclusion: A number of herbal medicines appear to be relatively safe and provide potential efficacy in amelioration of ADHD. However, due to lack of adequate reports of RCTs, no definitely specific recommendations could been made so far.
- Clinical evaluation of a topical Unani pharmacopoeial formulation
Tila-e-Kalf in the management of melasma (Kalf): A randomized controlled clinical trial Abstract: Objective: Melasma is a chronic, acquired, symmetrical hyper melanosis of skin, characterized by irregular light to dark brown patches on sun-exposed areas, with a significant effect on psychological health; melasma is termed as Kalf in Unani medicine. Conventional treatments have transitory results and often carry adverse effects like skin irritation, scarring, etc. This study was planned to evaluate the safety and efficacy of a Unani pharmacopoeial formulation Tila-e-Kalf, comprising of lentil (Lens culinaris), bitter almond (Prunus amygdalus), and fig (Ficus carica), and to compare its efficacy with standard drug hydroquinone in patients of melasma.
Materials and Methods: This was an 8-week open-label, standard controlled, randomized clinical study conducted on patients of epidermal melasma. The test group received Tila-e-Kalf while the control group received hydroquinone 4% cream for local application once daily. Efficacy was assessed by MASI (Melasma Area Severity Index), DLQI (Dermatology Life Quality Index), and PGA (Physician Global Assessment) and colored photographs.
Results: Mean MASI score decreased from10.65±0.85 to 7.07±0.74 in the test group (p<0.0001) and from 11.28±1.24 to 7.76±0.9 (p<0.0001) the in control group. Similar improvement was noticed in other parameters also. A large number of patients in the control group reported mild burning, itching, dryness, and skin rashes, while only one patient in the test group reported mild itching.
Conclusion: Tila-e-Kalf as a topical depigmenting agent was found equally effective with better tolerability and safety as compared to hydroquinone.
- “Ferula assa-foetida L” or “Foeniculum vulgare”' Which one is more
effective in the management of polycystic ovarian syndrome' A randomized, placebo controlled, triple-blinded Abstract: Objective: There are few evaluation about the effects of Fennel and Ferula on human polycystic ovary syndrome (PCOS). The goals of this study were to evaluate and compare the effectiveness of two medicinal plants of the Apiaceae family (Fennel and Ferula) in management of PCOS.
Materials and Methods: The sample size was 47 participants with PCOS who were randomly divided into 3 groups. The Ferula assa-foetida L group received 100 mg of Ferula (n=14), the Foeniculum vulgare group received 46 mg of Fennel (n=15), and the placebo group received placebo twice daily for 3 months (n=14).
Results: Before the intervention, there were no significant differences between groups in terms of clinical parameters, endometrial thickness, or ovarian volume. After the interventions, the number of ovarian follicles was decreased in the Ferula and Fennel groups as compared to the placebo group (p<0.05). The number of ovarian follicles in both ovaries in the Ferula and Fennel group decreased and this decrease was significant in the right side as compared to placebo group. Our findings showed significant changes in dehydroepiandrosterone sulfate (DEHAS) and thyroid-stimulating hormone (TSH) levels after the intervention (p<0.03) between the Ferula and Placebo groups.
Conclusion: Since use of Ferula could make significant changes in TSH and DEHAS levels and decrease the number of right and left ovarian follicles compared to Fennel and placebo, it can be concluded that this herbal medicine is more effective than Fennel in managing PCOS.
- Curcumin’s effect on serum zinc, copper and magnesium levels in
obese individuals Abstract: Objective: The obesity prevalence is growing worldwide. There is strong evidence indicating that a disturbance of zinc, copper and magnesium concentrations is associated with the development of obesity and its related diseases. Our aim was to determine the effect of curcumin supplementation on serum zinc, magnesium and copper in obese individuals.
Materials and Methods: In this randomized crossover trial study, thirty obese patients with an age range of 18 to 65 years were randomized to treatment with curcumin 1 g/day or placebo for 30 days. There was then a two-week wash-out period, after which, subjects crossed to the alternate regimen. Serum levels of zinc, copper and magnesium were determined at baseline and at the end of the study.
Results: The study groups were similar to each other in base line characteristics. We did not observe significant impacts (p>0.05) of curcumin on Cu, Zn, Mg serum concentrations.
Conclusion: Curcumin administration at a dose of 1 g/day for 30 days did not affect serum Cu, Zn, Mg levels in obese subjects.
- Nano-hesperetin ameliorates 6-hydroxydopamine-induced behavioral deficits
and oxidative damage by up-regulating gene expression of antioxidant enzymes Abstract: Objective: Hesperetin (Hst) has shown several pharmacological effects. The efficacy of Hst is highly restricted in vivo due mainly to poor bioavailability. This investigation was intended to compare the influence of Hst and nano-Hst treatment on 6-hydroxydopamine (6-OHDA)-induced behavioral deficits and oxidative stress in rats.
Materials and Methods: Forty-two Wistar male rats were equally assigned to 6 groups: control, 6-OHDA, Hst5, Hst10, nano-Hst5, and nano-Hst10. Treatment with Hst and nano-Hst was initiated 1 day after the intrastriatal injection of 6-OHDA and continued for 28 days. Behavioral deficits were evaluated using apomorphine-induced rotation test (AIRT), narrow beam test (NBT) and novel object recognition test (NORT), and the hippocampus and striatum were used to evaluate oxidative stress-related parameters.
Results: The rats injected only with 6-OHDA showed learning and memory deficits but Hst and nano-Hst treatments improved it (p<0.001). Compared to the control group, a marked promotion in Malondialdehyde (MDA) levels along with a marked reduction in activities and gene expression of antioxidant enzymes and reduced glutathione (GSH) levels in the hippocampus and striatum were observed in the 6-OHDA group (p<0.01). However, administration of Hst and nano-Hst remarkably diminished MDA levels (p<0.01), and significantly increased the activities (p<0.01) and gene expression of antioxidant enzymes (p<0.05) and GSH levels (p<0.01) compared to the 6-OHDA group. In most parameters, nano-Hst has shown better therapeutic effects than Hst.
Conclusion: Our findings reveal that Hst can be considered as a potential candidate for the treatment of neurodegenerative diseases and that nano-Hst may have better bioavailability.
- The effects of cinnamon supplementation on adipokines and
appetite-regulating hormones: A systematic review of randomized clinical trials Abstract: Objective: Cinnamon is extracted from the inner bark of Cinnamomum trees. Recent studies have indicated that cinnamon is a safe and cost-effective treatment for improving body weight, lipid profiles, insulin resistance, and blood pressure. This systematic review aimed to summarize the effect of cinnamon supplementation on adipokines and appetite-regulating hormones.
Materials and Methods: This comprehensive literature search was conducted using databases such as PubMed, Scopus, ISI Web of Science, and Google Scholar up to March 2022 without any limitation. The quality of eligible studies was evaluated through the Cochrane Collaboration’s tool for assessing the risk of bias.
Results: This systematic review included six clinical trial studies (363 participants), among which, only one study was performed on children, and two investigations were conducted on obese participants. A decreasing effect was found in the level of leptin and visfatin after cinnamon supplementation. Two out of three studies examined adiponectin levels and revealed non-significant effects of cinnamon consumption on this parameter. Two studies evaluated ghrelin levels and found an increase after cinnamon supplementation. The result of cinnamon supplementation on other biomarkers such as glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and resistin was inconsistent.
Conclusion: The result of this systematic review indicated the increasing effect of cinnamon supplementation on ghrelin levels and decreasing effect on leptin and visfatin levels. However, more clinical data are required to clarify the beneficial effects of cinnamon on adipokines levels due to the controversial findings of the studies.
- Evaluation of berberine pellet effect on clinical recovery time in
COVID-19 outpatients: A pilot clinical trial Abstract: Objective: Severe disease onset of COVID-19 may result in alveolar injury and respiratory failure. Apoptosis and inflammation are the main causes of respiratory distress syndrome. Berberine is used in medicine as an analgesic, anti-asthmatic, anti-inflammatory, and antiviral. In the current investigation, the effect of berberine on COVID-19 outpatients was studied.
Materials and Methods: The present clinical trial was performed on 40 outpatients who were randomly assigned to berberine (300 mg, TID, 2 weeks) (n=19) or placebo groups (n=21). Both groups received standard therapy and they were monitored on days 3, 7, and 14 after the beginning of the therapy for clinical symptoms’ improvement, quantitative CRP, lymphopenia, CBC, and SpO2. The severity and frequency of these symptoms and the level of the parameters were statistically compared between the two groups.
Results: On days (0, 3, 7, and 14, there was no significant difference between the berberine and placebo groups in the improvement of clinical symptoms (cough, shortness of breath, nausea, loss of smell and taste, diarrhea, dizziness, sore throat, stomachache, body aches, and body temperature), quantitative CRP, lymphopenia, WBC, neutrophils, platelets, or SpO2.
Conclusion: Berberine (300 mg, TID, two weeks) is ineffective in treating COVID-19. More research with a larger sample size is needed to investigate different berberine dosages in other pharmaceutical formulations.
- Antioxidant, cytotoxic, and genotoxic potentials of the gum of Ferula
gummosa Boiss on PC-3 cells Abstract: Objective: Ferula gummosa Boiss is a well-known Iranian endemic plant that has been used in Iranian traditional medicine against various diseases. This study aimed to evaluate the antioxidant and cytotoxic capacity of F. gummosa gum on prostate cancer PC-3 cells.
Materials and Methods: In this study, we evaluated the total phenolic and flavonoid contents, and antioxidant potentials of the gum. The MTT experiment was conducted to assess the cytotoxic potential of the gum on PC-3 cells. The clonogenic, micronucleus formation, and acridine orange/ethidium bromide staining methods were used to evaluate the survival and proliferation of PC-3 cells. DNA degradation and caspase 3/7 activity evaluations were used to assess apoptosis. The inhibitory effect on the migration of PC-3 cells was examined by in vitro wound-healing experiment.
Results: Total phenolic and flavonoid contents, and antioxidant potential of the gum were 9.22 mg of gallic acid equivalent (GAE)/g, 3.6 mg of quercetin equivalents (QE) /g of the extract, and 13 μg/ml, respectively (compared to gallic acid and quercetin, respectively) (p<0.05). The IC50 value was 9.14 µg/ml for 48 hours (compared to non-treated cells) (p<0.01). The pattern of DNA degradation, and caspase 3/7 activity levels (compared to non-treated cells) (p<0.05) proposed decreased cell viability that may be due to apoptosis induction. Microscopic observations revealed nuclear condensation, a significant increase in the formation of micronuclei, and inhibition of forming colonies (compared to non-treated cells) (p<0.01) in PC-3 cells treated with 8 and 10 μg/ml of the gum. Wound-healing assessment showed the migration suppression potentials of the gum (compared to non-treated cells) (p<0.05).
Conclusion: These results indicate that F. gummosa has considerable antioxidant and cytotoxic properties that can make it a good nominee for subsequent investigations.
- Lavender (Lavandula angustifolia) syrup as an adjunct to standard care in
patients with mild to moderate COVID-19: An open-label, randomized, controlled clinical trial Abstract: Objective: The ongoing COVID-19 pandemic has been associated with clinical signs characterized by fever, fatigue and cough. Our study aimed to assess the efficacy of a Persian medicine formulation, lavender syrup, as an add-on to standard care in patients with mild to moderate COVID-19.
Materials and Methods: In this clinical trial which was conducted in Gorgan (Iran), 84 male and female COVID-19 outpatients were randomly allocated to either lavender syrup receiving 9 ml/twice/day for 21 days with standard conventional care or control groups. The primary objectives were to assess the improvement of clinical symptoms, while the secondary objectives were treatment satisfaction and anxiety levels which were evaluated once a week for 3 weeks.
Results: Out of 84 participants, 81 were analyzed (41 in the add-on group). The comparison between groups for cough severity and anosmia showed a higher reduction in the lavender group. The effect size was 0.6 for cough relief. Other symptoms and the Hamilton total score decreased in both groups with no statistically significant differences between the groups. The lavender group showed greater patients’ satisfaction score.
Conclusion: Adjunctive therapy with lavender syrup could reduce cough and improve the quality of life in patients with COVID-19 patients.
- The use of Ephedra herbs in the treatment of COVID-19
Abstract: Objective: Ephedra herbs are the only extant genus in its family, Ephedraceae, and order, Ephedrales. It has been prescribed in traditional medicine for improving headaches and respiratory infections. On the other hand, because the coronavirus disease 2019 (COVID-19) causes respiratory problems and COVID-19 pandemic is the most widespread outbreak that has affected humanity in the last century, the current review aims using literature search to investigate the effects of the Ephedra herbs compounds on COVID-19 to supply a reference for its clinical application in the inhibition and remedy of COVID-19.
Materials and Methods: This review was performed using articles published in various databases, including Web of Science, PubMed, Scopus, and Google Scholar, without a time limit. For this paper, the following keywords were used: "Ephedra", "coronavirus disease 2019", "COVID-19", "Severe acute respiratory syndrome coronavirus 2" or "SARS CoV 2".
Results: The results of this review show that the Ephedra herbs have effectiveness on COVID-19 and its compounds can bind to angiotensin-converting enzyme 2 (ACE2) with a high affinity and act as a blocker and prevent the binding of the virus.
Conclusion: Some plants used in traditional medicine, including the Ephedra herbs, with their active compounds, can be considered a candidate with high potential for the control and prevention of COVID-19.
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