Effects of Dietary Modification Based on Complementary and Alternative Iranian Medicine in Patients with Secondary-Progressive Multiple Sclerosis: A Randomized Controlled Clinical Trial.

Objectives: To evaluate the efficacy of dietary modifications based on complementary and alternative Iranian medicine (CAIM) in patients with secondary-progressive multiple sclerosis (SPMS). Design: In this randomized controlled trial, 70 SPMS patients were randomized to receive either a moderate-nature diet based on Persian medicine (as intervention) or usual diet plus health-related diet recommendations (as control) for 2 months. Serum high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), Expanded Disability Status Scale (EDSS), Modified Fatigue Impact Scale (MFIS), State-Trait Anxiety Inventory (STAI), Global Pain Scale (GPS), Gastrointestinal Symptom Rating Scale (GSRS), anthropometric measurements, and quality of life (QOL) were assessed at baseline and end of trial. Analysis of covariance was performed, and the results were adjusted for potential confounders using SPSS v.14. Results: All participants completed the study for 2 months. There were significant improvements across the mean changes of hs-CRP (-0.1 ± 0.2 mg/L for intervention vs. -0.01 ± 0.13 mg/L for control; padjusted = 0.012), MFIS (-11.0 ± 11.8 vs. -0.7 ± 9.9; padjusted <0.001), GSRS (-19.9 ± 16.3 to 1.2 ± 17.5; padjusted <0.001), GPS (padjusted = 0.032), and QOL (padjusted <0.05). No significant difference was observed across the ESR, EDSS, STAI, and anthropometric measurements. Conclusion: Dietary modifications based on CAIM may improve inflammation and clinical manifestations in SPMS patients. Nonetheless, further trials are required to confirm these findings. Clinical Trial Registration: IRCT20181113041641N2.

The effect of Spirulina supplementation on lipid profile: GRADE-assessed systematic review and dose-response meta-analysis of data from randomized controlled trials.

BACKGROUND: Cardiovascular diseases (CVD) are one of the most important causes of death worldwide. Dyslipidemia is one of the main causal risk factors for CVD that can be controlled by modifying lifestyle, which entails the use of healthy diets containing functional foods. The present study was conducted to summarize the effects of Spirulina on the lipid profile in previous randomized controlled trials. METHODS: MEDLINE, Scopus, Clarivate Analytics Web of Science, and the Cochrane Library databases were searched systematically until January 2023, for clinical interventions that investigated the effect of Spirulina supplementation on plasma lipid profile concentrations. RESULTS: ooled results of 20 studies (with 23 arms and 1076 participants) indicated that Spirulina intervention significantly reduced LDL-C (SMD: -0.6, 95% CI: -0.9, -0.2, P<0.05), TC (SMD: -0.6, 95% CI: -0.9, -0.2, P<0.05) and TG (SMD: -0.6, 95% CI: -0.9, -0.2, P<0.05) levels while HDL-C levels were significantly increased (SMD: 0.3, 95% CI: 0.0, 0.6, P<0.05). CONCLUSIONS: The findings of the present meta-analysis and review show the usefulness of supplementing with Spirulina in improving serum levels of TC, TG, LDL-C, and HDL-C.

The effect of l-carnitine supplementation on mortality and clinical outcomes in ventilator-dependent critically ill patients with obesity and COVID-19: Protocol for a randomized double-blind placebo-controlled trial.

Background: Coronavirus disease 2019 (COVID-19) still remains a pandemic accounting for at least 15% of intensive care unit (ICU) admissions. Recently, it has been observed that l-carnitine levels, which play an important role in fatty acid metabolism, have an inverse association with the severity of COVID-19 and its complications, hence a potential role for supplementing with this nutraceutical has been suggested. The current protocol describes a trial aiming to an evaluation of the effect of l-carnitine intervention on mortality and clinical outcomes in ICU-admitted patients with COVID-19. Methods: This parallel-group, randomized, placebo-controlled, and double-blind clinical trial involves 50 participants and will be performed at the ICU of Artesh (AJA) Hospital, Mashhad, IRAN. Eligible participants will be randomized into two groups: 1) the intervention group will receive 1000 mg l-carnitine capsules 3 times a day, and 2) the placebo group will receive 1000 mg placebo capsules 3 times a day. Assessments will be performed at baseline, 7 and 28 days after study initiation. The primary outcome includes changes in serum levels of C-reactive protein (CRP). Secondary outcomes include the length of stay in the ICU, ICU mortality, hospital mortality, 28-day mortality, duration of mechanical ventilation (MV), and the neutrophil-lymphocyte ratio (NLR). Conclusion: Based on previous evidence, l-carnitine may reduce inflammation and oxidation stress and improve respiratory function. However, the effects of l-carnitine on ventilator-dependent COVID-19 critically ill patients have not been assessed yet, justifying the necessity to conduct a clinical study in this field. c.

An overview on role of nutrition on COVID-19 immunity: Accumulative review from available studies.

The novel coronavirus infection (COVID-19) conveys a serious global threat to health and economy. A common predisposing factor for development to serious progressive disease is presence of a low-grade inflammation, e.g., as seen in diabetes, metabolic syndrome, and heart failure. Micronutrient deficiencies may also contribute to the development of this state. Therefore, the aim of the present study is to explore the role of the nutrition to relieve progression of COVID-19. According PRISMA protocol, we conducted an online databases search including Scopus, PubMed, Google Scholar and web of science for published literatures in the era of COVID-19 Outbreak regarding to the status of nutrition and COVID-19 until December 2021. There were available studies (80 studies) providing direct evidence regarding the associations between the status of nutrition and COVID-19 infection. Adequate nutritional supply is essential for resistance against other viral infections and also for improvement of immune function and reduction of inflammation. Hence, it is suggested that nutritional intervention which secures an adequate status might protect against the novel coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome - coronavirus-2) and mitigate its course. We also recommend initiation of adequate nutritional supplementation in high-risk areas and/or soon after the time of suspected infection with SARS-CoV-2. Subjects in high-risk groups should have high priority for applying this nutritive adjuvant therapy that should be started prior to administration of specific and supportive medical measures.

Effect of a diet based on Iranian traditional medicine on inflammatory markers and clinical outcomes in COVID-19 patients: A double-blind, randomized, controlled trial.

Introduction: SARS-CoV-2 causes severe acute respiratory syndrome prompting worldwide demand for new antiviral treatments and supportive care for organ failure caused by this life-threatening virus. This study aimed to help develop a new Traditional Persian Medicine (TPM) -based drug and assess its efficacy and safety in COVID-19 patients with major symptoms. Methods: In February 2022, a randomized clinical trial was conducted among 160 patients with a confirmed diagnosis of COVID-19 admitted to Emam Reza (AJA) Hospital in Tehran, Iran. During their hospitalization, the intervention group received a treatment protocol approved by Iran's Ministry of Health and Medical Education (MOHME), consisting of an Iranian regimen, Ficus carica; Vitis vinifera, Safflower, Cicer arietinum, Descurainiasophia seeds, Ziziphus jujuba, chicken soup, barley soup, rose water, saffron, and cinnamon spices. All patients were compared in terms of demographics, clinical, and laboratory variables. Results: One hundred and sixty COVID-19 patients were divided into two groups: intervention and control. In baseline characteristics, there was no significant difference between the intervention and control groups (p>0.05). Using SPSS software version 22, statistical analysis revealed a significant difference in four symptoms: myalgia, weakness, headache, and cough (p<0.05). During the 5-day treatment period, the control group had significantly lower C-reactive protein (p<0.05). Conclusion: While more research with a larger sample size is needed, the proposed combination appears to be effective in the treatment of symptoms as well as inflammatory biomarkers such as C-reactive protein in COVID-19 patients.Iranian registry of clinical trials (IRCT) IRCT20220227054140N1.

The effect of Nigella sativa oil on vascular dysfunction assessed by flow-mediated dilation and vascular-related biomarkers in subject with cardiovascular disease risk factors: A randomized controlled trial.

Cardiovascular diseases (CVD) are the leading causes of mortality worldwide. Flow-mediated dilation (FMD) is a marker of vascular function. Beneficial cardiometabolic effects of Nigella sativa (N. sativa) have been observed. We evaluated the effect of N. sativa oil on FMD, plasma nitrite, and nitrate (NOx) as nitric oxide (NO) metabolites, and inflammatory markers in subjects with CVD risk factors. Fifty participants were randomly assigned to either the N. sativa (two capsules of 500 mg N. sativa oil) or the placebo group (two capsules of 500 mg mineral oil), for 2 months. The brachial FMD, plasma NOx, vascular cellular adhesion molecule-1 (VCAM-1), and intracellular adhesion molecule-1 (ICAM-1) were measured. FMD and plasma NOx levels was significantly increased in the N. sativa group compared to the placebo group (changes: 2.97 ± 2.11% vs. 0.71 ± 3.19%, p < 0.001 for FMD and 4.73 ± 7.25 µmol/L vs. 0.99 ± 5.37 µmol/L, p = 0.036 for plasma NOx). However, there was no significant difference in ICAM-1 and VCAM-1 levels between groups. Therefore, N. sativa oil improves vascular NO and FMD in subjects with cardiovascular risk factors. However, more studies are warranted to confirm the beneficial impacts of the N. sativa oil on vascular inflammation.

The effect of ginger supplementation on metabolic profiles in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: There is some evidence regarding the positive effects of ginger supplementation on metabolic profile in patients with type 2 diabetes (T2DM). However, they are conflicting. The present systematic review and meta-analysis aimed to summarize earlier findings for the effect of ginger supplementation on metabolic profile in patients with T2DM. METHODS: Scopus, PubMed and Google Scholar databases were systematically searched up until September 2021 to collect all randomized clinical trials that evaluated the effect of ginger supplementation on FBS, HbA1c, TC, TG, LDL, HDL, SBP and DBP in patients with T2DM. We conducted our study according to the 2020 PRISMA guidelines. We included only English language publications. Pooled effect sizes were measured using a random-effects model and were reported as the weighted mean difference (WMD) and 95% CI. In addition, the Cochrane Collaboration's risk of bias tool was used to evaluate quality of the trials. RESULTS: In overall, 10 articles were included in this systematic review and meta-analysis. Our pooled meta-analysis indicated a significant reduction in FBS following ginger supplementation by polling 8 effect sizes [weighted mean difference (WMD): - 18.81; 95% CI: - 28.70, - 8.92), I2 = 77.4%] and in HbA1C through 7 effect sizes (WMD: -0.57; 95% CI: -0.93, -0.20, I2 =88.6%). Pooling 5 effect sizes, we found a significant reduction in SBP (WMD: -4.20; 95% CI: -7.64, -0.77, I2 =97%) and DBP [WMD: - 1.61; 95% CI: - 3.04, - 0.18), I2 = 93.2%] after supplementation with ginger. However, our pooled meta-analysis indicated that ginger supplementation had no significant influence on lipid profile involving TG, TC, LDL and HDL. CONCLUSIONS: We found significant reductions in FBS, HbA1C, SBP and DBP after supplementation with ginger in patients with T2DM compared to control group, with no significant changes in serum lipids. Further large RCTs are required to shed light on this issue.

Analgesic and anti-inflammatory properties of hydroalcoholic extracts of Malva sylvestris, Carum carvi or Medicago sativa, and their combination in a rat model.

OBJECTIVE: The aim of this study was to evaluate the analgesic and anti-inflammatory effects of the hydroalcoholic extracts of Malva sylvestris flowers or Carum carvi and Medicago sativa seeds, alone and in combination, which have been used in traditional Iranian medicine. METHODS: Male Wistar rats were divided into 6 treatment groups: distilled water, sodium salicylate (SS), M. sylvestris extract (600 mg/kg), C. carvi extract (600 mg/kg), M. sativa extract (300 mg/kg) and combined extract (including 300 mg/kg M. sylvestris and C. carvi extracts, and 150 mg/kg M. sativa extract). The formalin pain model was used to evaluate the antinociceptive effects of the treatments. For anti-inflammatory effect, acute (one hour after injection) and chronic (during a week after injection) paw inflammation was measured after subcutaneous injection of 2.5% formalin in the hindpaw. Finally, tissue samples from all groups were prepared for histopathological studies. RESULTS: The combined extract significantly inhibited the nociception in the acute phase of the formalin test (P < 0.001). In the chronic phase, all the extracts and SS had significant analgesic effect (P < 0.001). Analgesic activity of the combined extract was significantly stronger than SS (P < 0.01). In the acute inflammation model, M. sylvestris, C. carvi and the combined drug had significant inhibitory effects against paw edema (P < 0.05). All extracts, individually and in combination, significantly alleviated chronic paw inflammation (P < 0.01). The combined extract had much more anti-inflammatory activity than SS (P < 0.05). Histopathological results indicated improvement and reduction of inflammatory factors in the treatment groups. CONCLUSION: M. sylvestris, C. carvi and M. sativa have analgesic and anti-inflammatory properties. Potentially, each of these extracts or a mixture of them might be a valuable alternative drug to control pain and inflammation.

Determination of total phenolic content, antioxidant activity and antifungal effects of Thymus vulgaris, Trachyspermum ammi and Trigonella foenum-graecum extracts on growth of Fusarium solani.

Ajowan, thyme and fenugreek are spice and aromatic crops with a number of medicinal properties which are known as important sources of essential phytochemicals. The purpose of this study was to investigate the antioxidant capacity, total phenolic content and antifungal activities of these plant extracts on growth of Fusarium solani, an important plant pathogen, soil saprophyte and one of the causal agents of fusariosis in human and animals. Their total antioxidant activity was measured using DPPH radical scavenging assay and their antimicrobial activity was determined through poison food assay at two concentrations (1000 and 1500 ppm) and spore germination assay in vitro. All methanolic extracts showed high antioxidant activity which among them methanolic extract of thyme demonstrated higher antioxidant potential with a low IC50 (16.50 mg ascorbic acid/g). Also, the highest phenolic content (70.55 mg GAE g-1) was observed in methanolic extract of thyme. The highest and lowest amount of thymol was determined in methanolic extract of thyme and aqueous extract of ajowan. Methanolic extracts of thyme leaves and ajowan seeds at concentration of 1500 ppm were potentially effective against F. solani over the control treatments by 90.33% and 85.73%, respectively. Followed by hydro-ethanolic and aqueous extracts exhibited a lesser percentage of inhibition. The MIC value for methanolic extract of thyme and ajowan was 3.75 mg/ml followed by hydro-ethanolic and aqueous extracts, respectively. The amount of calculated MFC was ranging from 7.5 to 30 mg/ml for thyme methanolic and fenugreek aqueous extracts, respectively.

Antifungal activity of the essential oils of some medicinal plants against human and plant fungal pathogens.

The present study was conducted to assess the antifungal activity of essential oils of medicinal plants Mentha piperita (peppermint), Foeniculum vulgare, Satureja hortensis (Savory), Ferula asafoetida and Cuminum cyminum against Alternaria sp., Bipolaris sorokiniana and Acremonium sclerotigenum. The antifungal activity was evaluated by Broth Microdilution Method. Minimum Inhibitory Concentration (MICs) and Minimum Fungicidal Concentration (MFCs) of the essential oils were compared with Amphotricin B and Captan as standard drug. MIC values for all essential oils were between 1 to 8 mg/mL. MIC value of Fennel essential oil was comparable to MFC value obtained from fungicide Captan. Peppermint essential oil exhibited maximum inhibitory and fungicide activity in concentrations of 2 mg/ml and 4 mg/ml against Alternaria sp. The essential oil was more effective than Fennel against Bipolaris, but MFC values of both essential oils were 4 mg/ml. C. cyminum displayed less susceptibility against all of the fungi. Regarding our finding, peppermint and Fennel oil seem to be a promising solution to control plant diseases.

Effect of ischemia preconditioning and leech therapy on cutaneous pedicle flaps subjected to prolonged ischemia in a mouse model.

We sought to determine the effect of ischemic preconditioning (IPC) and hirudotherapy (leech therapy) on cutaneous pedicle flaps after they underwent prolonged ischemia (global ischemia) in a mouse model. Twenty cutaneous pedicle flaps were elevated in 20 mice, and the animals were randomized into four groups: sham, control, IPC and leech (5 flaps in each group). Except in the sham group, all flaps were subjected to global ischemia for 5 h via pedicle clamping. The control group did not receive any treatment before or after global ischemia. In the IPC group, global ischemia was preceded by three 10-min episodes of ischemia, each followed by 10 min of reperfusion. In the leech therapy group, after global ischemia, hirudotherapy was performed. Flap survival area and histopathological changes were evaluated on the 10th day after surgery. Flap survival areas were significantly higher in both the IPC and leech groups than in the control group and were significantly higher in the leech group than in the IPC group (p < 0.05). In conclusion IPC and hirudotherapy had definite effects on the survival area of cutaneous pedicle flaps that underwent prolonged ischemia in a mouse model.

Leech therapy for linear incisional skin-wound healing in rats.

BACKGROUND: The aim of this study was to investigate the effects of leech therapy (LT), in comparison with topical phenytoin (PHT), on incisional skin-wound healing in animal models. METHODS: This experimental study included 15 male rats (5 animals in 3 groups) with approximately equal body weights (350 ± 10 g). Skin wounds with lengths of 20 mm and depths of 0.5 mm were made on the dorsolateral region of rats 4 cm from the spine. The first group (PHT group) was treated daily with topical PHT (1%) while the second group (LT group) received LT at the beginning of the experiment. The control group received neither the drug nor the therapy. Wound healing was evaluated every day, and the study was continued until the wound had completely healed. Changes in the areas and the appearances of the skin wounds and histological differences (at the end of the experiment) were used to investigate the differences in wound healing among the groups. RESULTS: The process of wound healing was significantly faster in the group treated with LT (p < 0.05) than in the group treated with the PHT. CONCLUSION: The study results showed that LT improved incisional skin-wound healing in rats.

Acute and subchronic toxicological evaluation of Echinophora platyloba DC (Apiaceae) total extract in Wistar rats.

OBJECTIVE: Echinophora platyloba DC is a widely used herbal medicine and food seasoning in Iran. It is claimed to exert antimicrobial, antifungal, and antispasmodic effects. Despite the prevalent use of this plant as a food and medicine, there are no reports on its possible toxic effects. To evaluate the safety of E. platyloba, we tested its acute and sub-chronic toxicity in male and female Wistar rats. METHODS: Rats were orally treated with four different single doses of E. platyloba total extract and screened for signs of toxicity two weeks after administration. In the sub-chronic toxicity study, E. platyloba was administered for 45 days. Mortality, clinical signs, body weight changes, hematological and biochemical parameters, gross findings, organ weights, and histological markers were monitored during the study. RESULTS: We found no mortality and no abnormality in clinical signs, body weight, or necropsy findings in any of the animals in the acute study. The results of the subchronic study showed no significant difference in hematological parameters in either sex. There was a significant increase in lactate dehydrogenase in the female groups. A significant increase in the relative lung weight of female rats was noted at 500 mg/kg. Histopathological examinations revealed intra-alveolar hemorrhage in the male rats (500 mg/kg). In the females, congestion of the alveolar capillaries (at 500 mg/kg) and liver bridging necrosis (at 200 mg/kg) were significantly increased. CONCLUSION: The no observed adverse effect level of E. platyloba was determined to be 200 and 50 mg/kg for male and female rats, respectively.

Acute and subchronic toxicological evaluation of Echinophora platyloba DC (Apiaceae) total extract in Wistar rats

OBJECTIVE: Echinophora platyloba DC is a widely used herbal medicine and food seasoning in Iran. It is claimed to exert antimicrobial, antifungal, and antispasmodic effects. Despite the prevalent use of this plant as a food and medicine, there are no reports on its possible toxic effects. To evaluate the safety of E. platyloba, we tested its acute and sub-chronic toxicity in male and female Wistar rats. METHODS: Rats were orally treated with four different single doses of E. platyloba total extract and screened for signs of toxicity two weeks after administration. In the sub-chronic toxicity study, E. platyloba was administered for 45 days. Mortality, clinical signs, body weight changes, hematological and biochemical parameters, gross findings, organ weights, and histological markers were monitored during the study. RESULTS: We found no mortality and no abnormality in clinical signs, body weight, or necropsy findings in any of the animals in the acute study. The results of the subchronic study showed no significant difference in hematological parameters in either sex. There was a significant increase in lactate dehydrogenase in the female groups. A significant increase in the relative lung weight of female rats was noted at 500 mg/kg. Histopathological examinations revealed intra-alveolar hemorrhage in the male rats (500 mg/kg). In the females, congestion of the alveolar capillaries (at 500 mg/kg) and liver bridging necrosis (at 200 mg/kg) were significantly increased. CONCLUSION: The no observed adverse effect level of E. platyloba was determined to be 200 and 50 mg/kg for male and female rats, respectively.

The effect of "Teucrium polium L." extracts on insulin release from in situ isolated perfused rat pancreas in a newly modified isolation method: the role of Ca2+ and K+ channels.

BACKGROUND: "Teucrium polium L." (TP) has been long recommended in Iranian folk medicine for its anti-diabetic activities. We attempt here to evaluate the effect of TP extract on insulin secretion in rat pancreas. METHODS: Rat pancreas was isolated in situ and perfused with Krebs solution containing low glucose (LG, 2.8 mM) or high glucose (HG, 16.7 mM) as perfusate. The aqueous extract (Aq. E) and methanolic extract (Met. E) of TP aerial parts and two partition fractions of Met. E were added to perfusate to evaluate insulin release. Diazoxide (DZX) and verapamil (VPM) were also used for assessing the probable mechanism of the effects. In each experimental group, the peak and baseline of insulin levels in effluent samples were compared. The GC/MS analysis was carried out to detect active ingredients in the extracts. RESULTS: Adding Met. E to the LG caused a significant increase (P<0.05) in insulin release from the basal level of 0.17 ± 0.05 µg/l to a peak value of 3.94 ± 1.29 µg/l. when Met. E was introduced to the HG, there was a further protracted stimulation of insulin release from 2.15 ± 1.35 µg/l to 6.16 ± 0.52 µg/l. Both DZX and VPM when added separately to the LG, led to inhibition of Met. E induced insulin secretion. The Aq. E and fractions had no significant effect on insulin secretion. Only in the Met. E, the component 5-hydroxy-4',7-dimethoxyflavone (apigenin-4',7-dimethylether) was detected. CONCLUSION: It can be concluded that the insulinotropic properties of TP extracts can be attributed to the presence of apigenin existing only in Met. E, but not in Aq. E and fractions. Moreover, certain types of K+ and Ca2+ channels take part in this effect.