Objectives We will evaluate the efficacy and safety of Melatonin, compared to the standard therapeutic regimen on clinical symptoms and serum inflammatory parameters in patients with confirmed COVID-19, who are moderately ill. Trial design This is a single-center, randomized, double-blind, placebo-controlled clinical trial with a parallel-group design conducted at Shahid Mohammadi Hospital, Bandar Abbas, Iran. Participants All patients admitted to Severe Acute Respiratory Syndrome Departments of Shahid Mohammadi Hospital, Bandar Abbas, Iran will be screened for the following criteria. Inclusion criteria: 1. Age ≥20 years 2. Confirmed SARS-CoV-2 diagnosis (positive polymerase chain reaction). 3. Moderate COVID-19 pneumonia (via computed tomography and or X-ray imaging), requiring hospitalization. 4. Hospitalized ≤48 hours. 5. Signing informed consent and willingness of the participant to accept randomization to any assigned treatment arm. Exclusion criteria: 1. Underlying diseases, including chronic hypertension, diabetes mellitus, seizure, depression, chronic hepatitis, cirrhosis, and cholestatic liver diseases. 2. Severe and critical COVID-19 pneumonia. 3. Use of warfarin, corticosteroids, hormonal drugs, alcohol, other antiviral and investigational medicines, and illegal drugs (during the last 30 days). 4. History of known allergy to Melatonin. 5. Pregnancy and breastfeeding. Intervention and comparator Intervention group: The standard treatment regimen for COVID-19, according to the Iranian Ministry of Health and Medical Education's protocol, along with Melatonin capsules at a dose of 50 mg daily for a period of seven days. Control group: The standard therapeutic regimen for COVID-19 along with Melatonin-like placebo capsules at a dose of one capsule daily for a period of seven days. Both Melatonin and placebo capsules were prepared at the Faculty of Pharmacy and Pharmaceutical Sciences, Hormozgan University of Medical Sciences, Bandar Abbas, Iran. Main outcomes The primary outcomes are the recovery rate of clinical symptoms and oxygen saturation as well as improvement of serum inflammatory parameters, including C-reactive protein, tumor necrosis factor-alpha (TNF-ɑ), interleukin-1β (IL-1β), and IL-6 within seven days of randomization. The secondary outcomes are the time to improve clinical and paraclinical features along with the incidence of serious adverse drug reactions within seven days of randomization. Randomization Included patients will be allocated to one of the study arms using block randomization in a 1:1 ratio (each block consists of 10 patients). This randomization method ensures a balanced allocation between the arms during the study. A web-based system will generate random numbers for the allocation sequence and concealment of participants. Each number relates to one of the study arms. Blinding (masking) All study participants, clinicians, nurses, research coordinators, and those analyzing the data are blinded to the group assignment. Numbers to be randomized (sample size) A total of 60 patients randomized into two groups (30 in each group). Trial Status The trial protocol is Version 1.0, August 14, 2020. Recruitment began August 22, 2020, and is anticipated to be completed by November 30, 2020. Trial registration The trial protocol has been registered in the Iranian Registry of Clinical Trials (IRCT). The registration number is “IRCT20200506047323N5”. The registration date was 14 August 2020. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

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Cancer and diabetes, the two mitochondria‐related diseases, have recently been linked to silent mating‐type information regulation 2 homolog 3 (SIRT3) activity irregularities. In this study, the effect of metformin, an antidiabetic with anticancer properties, has been evaluated on mitochondrial functionality markers, cell death pathways, and SIRT3 enzyme activity in the colon cancer cell line, HT‐29, and human embryonic kidney cells (HEK 293). HT‐29 cells were treated with metformin (5, 10, 20, 40, and 80 µM) for 24, 48, and 72 h for measuring the IC50 concentration. Reactive oxygen species (ROS) production, apoptosis, mitochondrial membrane potential, SIRT3 activity, and expression were evaluated against the colon cancer cell line, HT‐29. Results indicated a higher ROS production at 6 than 12 h with metformin treatment. Metformin modified the mitochondrial membrane potential, resulting in cell death induction. Results from SIRT3 activity and expression showed that metformin increased its activity and expression in cancer cells. In conclusion, metformin in HT‐29 cells disturbed the mitochondrial activity via increased ROS levels and SIRT3 activity, and these rapid modifications may play a key role in its cytotoxic property.

Objective To investigate the effects of hydroalcoholic extract of Ziziphus jujuba on the histopathological, tissue oxidative stress and inflammation plus to antioxidant pathways of colon tissue in rat with induced Ulcerative colitis. Materials and methods Ulcerative colitis was induced in 80 rats those divided into 8 equal groups. Group 1 and 2 were negative controls receiving 1 mL/day of normal saline in enema and oral; group 3 and 4 as positive control 1 and 2 received 10 mg/kg of intra-colonic asacol and oral mesalazine; groups 5 and 6 received 20% and 40% of hydroalcoholic extract of Z. jujuba trans-rectally; group 7 and 8 received 1500 and 3000 mg/kg of hydroalcoholic extract of Z. jujuba orally, respectively. After 7 days, animals were evaluated for colon tissue histopathology, levels of malondialdehyde and IL-1β, and activities of superoxide dismutase, glutathione peroxidase and myeloperoxidase in colon tissue. Results Hydroalcoholic extract of Z. jujuba in both forms of trans-rectal and oral administration especially in the higher doses could result into a more healing effect in damaged colonic tissue, more reduce glutathione peroxidase and IL-1β level. Also, these two doses (gel 40% and oral 3000 mg/kg) could more decrease the myeloperoxidase activity and stimulate superoxide dismutase and glutathione peroxidase activities. Also, gel 40% in transrectal administration was more potent than administration 3000 mg/kg in oral. Conclusion The results of the present study indicated that Z. jujube may be considered as a treatment of choice for Ulcerative colitis especially in gel form and also in dose-dependent pattern.

Background. The unresponsiveness to conventional pharmacological treatments and their side effects have led patients with irritable bowel syndrome (IBS) to use complementary and alternative medicine such as herbal remedies. Beside, Zataria multiflora Boiss (ZM), Trachyspermum ammi L. (TA), and Anethum graveolens L. (AG) are being used as an antiseptic, carminative, and antispasmodic in traditional medicine. This trial investigated the efficacy and safety of a combination of ZM, AG, and TA essential oils in the treatment of IBS. Method. The present study was a randomized double-blind clinical trial with parallel groups in Iran. Patients in the control arm received three tablets of 10 mg hyoscine butylbromide daily for two weeks, and the intervention arm was daily treated with two 250 mg softgel capsules containing 180 mg of essential oils of ZM, AG, and TA for two weeks. Primary outcomes were the response rates based on the IBS Symptom Severity Scale (IBS-SSS), IBS Adequate Relief (IBS-AR), and IBS Global Assessment Improvement (IBS-GAI) at the end and two weeks after the end of the intervention. Secondary outcomes were the improvement rates in IBS-SSS scores, improving the quality of life, safety, and tolerability. Results. The posttreatment improvement percentage based on IBS-AR, IBS-GAI, and IBS-SSS scales was 83.9%, 75%, and 87% in the intervention group and 37.9%, 27.5%, and 34.4% in the control group, respectively (P<0.001). Also, the improvement of the quality of life in the herbal medicine arm was significantly more than that in the control arm (P<0.001). Conclusions. According to the results, the herbal medicine investigated in this study can be considered an appropriate alternative treatment for IBS.