The novel targets considered in the recent research related to the treatment of depression include connexins, peroxisome proliferator activated receptor (PPAR), ω-3 fatty acids, ceramides, and renin–angiotensin–aldosterone system (RAAS). The major associated brain parts considered include hypothalamus, pituitary, and adrenal gland (HPA) axis in psychiatric disorders. The present review has proposed hypotheses such as combining PPAR (α/γ) agonist with noradrenaline dopamine reuptake inhibitor, gap junction channel modulator/hemichannel inhibitor with N-methyl-D-aspartate receptor antagonist like ketamine, ω-3 fatty acids derivatives like resolvin with tricyclic antidepressant like amineptine, RAAS-modifying drugs with serotonin reuptake inhibitors such as fluoxetine, ceramide synthase inhibitor/acid sphingomyelinase inhibitor with doxepin, and HPA axis-modifying drugs with bupropion. Further assessment of these combination approaches may help in availing better therapeutic options in the treatment of depression.

When antibiotics emerged, they gained lots of interest on the basis that they could protect and help human beings against a variety of bacterial diseases. These include urinary tract infections, pneumonia, sinus infections, etc. However, they have the potential to cause undeniable side effects including the drastic alter of gut microbiota. Antibiotic-associated diarrhea, nausea, vomiting, and other gastrointestinal side effects could also result from these alterations in gut microbiota. To diminish these side effects, the use of probiotics was proposed. Probiotics are defined as live microorganisms that have health benefits for the host by countervailing the bacteria which were lost in the gut, and they can be gained through different resources such as supplemented capsules and foods (especially dairy products). In this review, we discussed the antibiotic-associated side effects which can be treated or prevented by consuming probiotic foods.

Introduction: Falcaria vulgaris Bernh (FV) is a plant of the Apiaceae (Umbelliferae) family, which is known as Ghaziaghi in the Iranian Azeri language and Paghaza in the west of Iran. This plant is usually consumed in spring as a local vegetable and food. FV is recommended by traditional medicine resources for the treatment of skin diseases, gastrointestinal complaints, liver disease, blood purification, and increasing breast milk. The presence of tannins and saponins and the absence of flavonoids and terpenoids have been shown in FV. As various significant properties and special characteristics of FV have been expressed in numerous studies, this study aimed to collect documents and summarize and classify the properties of this plant through a systematic review method. Materials and Methods: We extracted 304 articles by searching electronic databases using the following keywords: “Paghazeh,” “Ghaziaghi,” “Falcaria vulgaris Bernh,” and “qazayagi.” Then, after eliminating duplicates and unrelated studies, finally, 19 studies were entered into a systematic review. Results: Significant therapeutic effects have been reported for FV through studies investigating the medicinal properties of the plant, including antioxidant, antimicrobial and antidiabetic effects, healing properties of skin and stomach ulcers, and protection of the liver and kidney. Most of these effects are related to antioxidant content and the presence of tannins and saponins in the plant. Conclusion: FV has significant effects on treatment of various diseases in animal studies and can be concluded in human clinical trials.

Though the scientific community of the entire world has been struggling to create preventive and therapeutic drugs for coronavirus disease 2019 (COVID-19), the role of nutraceuticals has been hitherto neglected. Established role of fatty acids and polyphenols in combating lifestyle disease can be harnessed to play a significant role in the prevention of this disease. The synergistic effect of these phytonutrients and prebiotics is anticipated to prove beneficial for prevention as well as attenuation of COVID-19 infection. Presence of fatty acids, polyphenols and prebiotics in vegetables from the Cucurbitaceae family makes them an attractive choice for being used as a nutritional supplement during COVID-19. These are known to attenuate the excessive immune response which may prove to be beneficial in preventing and mitigating COVID-19. Use of prebiotics to promote the growth of probiotics has also been recommended for the prevention and cure of COVID-19. However, no such report exists in literature that throws light on such role of cucurbita plants. The present review focuses on the role of the triad of fatty acids, prebiotics and polyphenols present in cucurbita plants in controlling systemic inflammation and endothelial damage, the two main etiopathological factors involved in COVID-19. Cucurbita plants are rich in all these components and their inclusion in diet would be an effective strategy to combat COVID-19. The main focus of the review is to discuss the role of various components of the plants of Cucurbita family, taken as dietary component, in prevention and control of the ongoing pandemic COVID19.

Aim: This study aims on the development of a chemometric-assisted spectroscopic method for the analysis of combined dosage form of emtricitabine (EMT), tenofovir alafenamide fumarate (TEN), and dolutegravir sodium (DOL). The use of a multivariate algorithm to analyse spectrophotometric data is a novel approach to estimating drug concentrations in formulations. Materials and Methods: The quantitative estimation of EMT, TEN, and DOL in tablets was carried out using four chemometric approaches: Classical least square (CLS), inverse least square, partial least square, and principal component regression. Thirty-two ternary mixtures of calibration sets and 16 mixtures of validation sets were prepared. The absorbance data matrix was attained by calculating absorbance at 25 different wavelengths in a range of 240–336 nm (Δλ = 4 nm). The chemometric calculations were performed using Matlab2018a and Minitab software. The developed methods were validated. Results: The great accuracy of the current study was justified by the near-perfect recovery values (100%) and low standard deviation. For chemometrics approaches, the root mean square error of calibration (RMSEC), root mean square error of prediction (RMSEP), and root mean square error of cross-validation (RMSECV) outcomes display decent accuracy and precision. Conclusion: The CLS approach yielded the lowest predicted residual error sum of squares, RMSEC, RMSEP, and RMSECV scores. As a result, CLS might be regarded as the best chemometric approach among all techniques utilized. The label claim determined is in excellent accordance with the mean recoveries for EMT, TEN, and DOL. So, it can be used in quality control laboratories.

Introduction: Methotrexate (MTX) is used as a folic acid antagonist in the treatment of many human cancers. Attachment of hydrophilic ligands to MTX improves its efficacy due to reducing toxicity and enzymatic degradation and it also increases its in-vivo half-life. Materials and Methods: In the present study, pH-responsive nanoconjugates of methoxy poly(ethylene glycol)-glutamic acid methotrexate (mPEG-Glu-MTX) have been prepared and characterized using hydrogen nuclear magnetic resonance (¹H-NMR) and Fourier transform infrared (FT-IR). Glutamic acid is attached to the mPEG chain by the carboxylic group and to the MTX via an amide bond to the amine group. Results: The prepared nanoconjugate has the mean diameter ranging from 160 to 190 nm and, the drug release was significantly induced two times at the pH of 5.5 and 3.5 compared with pH 7.4 (P < 0.05). The prepared mPEG-Glu-MTX nanoconjugate showed toxicity similar to AGS, MDA, and MCF7 cell lines compared with the free form of MTX (P > 0.1), which indicates that the conjugation does not effect on the MTX cytotoxicity but is expected to be successful in the targeted delivery of MTX. Conclusion: The results show that manufactured nanoconjugates can be considered as an efficient drug delivery system in the treatment of cancer; however, further studies are needed on the targeting activity of this nanocarrier in in-vivo conditions.

Background: Interferon-alpha (IFN-α) is a useful therapy for some types of cancers and viral infections. Cyclosporine A (CSA) is an immunosuppressant drug used to reduce the risk of graft rejection. Chronic use of IFN-α and CSA are related to psychological symptoms such as depression. Vanillic acid (VA) is a naturally occurring flavoring substance with antidepressant potential. The aim of this study was to evaluate the effect of VA on depression caused by these two drugs in a mice model. Materials and Methods: Male Swiss mice (25–30 g) were used. Depression was induced by IFN-α 1600000 IU/kg, sc for six days, or CSA20 mg/kg, ip for 3 days as VA 25 mg/kg, and pretreatment was ip injected. After evaluating the locomotor activity, depression was assessed by forced swimming test (FST) and sucrose preference (SP) test. Results: The selected treatments did not cause significant changes in the locomotor activity. IFN-α significantly increased the immobility time during FST (184.5 ± 12.9 s vs. vehicle 107.1 ± 11.4s) indicating depressive-like effect, and VA pretreatment reversed it (94.8 ± 17.8 s vs. IFN-α), SP increased to 76%. CSA also increased the immobility time during FST (160.3 ± 3.4 s vs. vehicle 113.2 ± 7.6 s; P < 0.05), VA pretreatment reduced it (81.8 ± 16.9 s, vs. cyclosporine; P < 0.001), and SP increased from 38% to 75%. SP results were in agreement with FST results. Conclusion: VA showed useful effect against IFN-α and cyclosporine-induced depression in mice. Further clinical studies regarding VA antidepressant effect in patients receiving IFN-α or CSA are warranted.

Purpose: Artemisia is an important genus of Iranian flora. The current study on the aerial parts of A. turanica was conducted to determine the most potent extract and its fractions in the cytotoxic assays. Materials and Methods: The cytotoxic effects of 13 fractions (1–13) from dichloromethane extract on three cancer cell lines (KB, HeLa, and U87MG) were assessed. Preliminary phytochemical analysis of more potent cytotoxic fractions was carried out using thin-layer chromatography (TLC) and different spray reagents. Results: Dichloromethane extract showed the best bioactivity against cancerous cell lines. Fractions 4, 6, 7, and 9 of this extract had potential effective components in the inhibition of the proliferation of KB cancer cells. In addition, fractions 4 and 6 were able to inhibit the growth of HeLa cell line. The active fractions decreased the mitochondrial membrane potential level, and played a critical role in caspase-3 and 9 activation and generation of reactive oxygen species. The cytotoxic activity of these fractions was found to be not significant toward U87MG cells. TLC analysis suggested the probable presence of terpenoids as the main component of most of the selected fractions. Conclusion: The species is suggested as the potential source of cytotoxic phytochemicals.

The goal of this research is the localization of hydroquinone (HQ) to the epidermis for the treatment of hyperpigmentation in rat skin. For this purpose, nanostructured lipid carrier (NLC) was selected for the dermal delivery of HQ. A 2³ factorial design was used in this study, and eight NLCs were prepared with a cold homogenization technique. HQ entrapment efficiency (EE %), particle size, morphology, thermal behavior of NLCs, and permeability parameters through rat skin with NLC in comparison with HQ aqueous solution (HQ-S) with Franz diffusion cells were evaluated. Based on the optimization technique, the best NLC was selected and in the in vivo experiment, the depigmentation effect of optimized NLC in comparison with that of HQ-S was evaluated. The results showed that the main problem for HQ permeability was fast permeation and low concentration in the site of action. Partitioning from aqueous donor phase into skin rate was the limiting step for drug flux, and this can be solved using NLC. The decrease in maximum flux obtained by NLC was according to formulation 8. Regression analysis suggested a significant and direct effect of the S/L ratio and the percentage of liquid lipids on the drug loading. NLC decreased drug permeation through rat skin basically due to sustained release properties.

Objective: Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases that affects 5%–10% of women of childbearing age. Several factors contribute to the development of PCOS such as dysfunction of the hypothalamic–pituitary axis and ovarian function, as well as increased insulin levels. The manifestations of the disorder include a wide range of symptoms, including menstrual disorders, acne, infertility, and increased body fat. Currently, the most well-known treatments for PCOS are clomiphene, metformin, letrozole, and tamoxifen. Due to their side effects, the identification of substitute drugs is essential. One of the traditional medicines, which is usually used in different parts of the world, particularly in Western Europe, is Bryonia dioica Jacq. (B. dioica). This plant is used in the treatment of disease due to its active ingredients like polyphenols. Materials and Methods: Induction PCOS in a female rat (3 weeks old) was performed through subcutaneous injection of testosterone enanthate (1 mg/100g) daily for 35 days. The effects of B. dioica (30 and 60 mg/kg) root methanolic extract on PCOS-induced was evaluated after 28-day treatment. On the last day, the serum levels of follicle-stimulating hormone (FSH), glucose, low-density lipoprotein/high-density lipoprotein (LDL/HDL), luteinizing hormone (LH), and testosterone and histological studies (hematoxylin and eosin [H&E] staining) were measured. Results: Results showed that FSH and LH levels (P < 0.05) as well as glucose (P < 0.001) in the B. dioica groups normalized significantly compared to the PCOS group. LDL levels decreased in rats and the LDL/HDL ratio decreased in all treatment groups. In histologic assay, metformin and B. dioica restricted the effects of testosterone in the ovaries of rats. Conclusion: The data indicate that methanolic extract of B. dioica recovers hormonal factors in PCOS.

Background: The effort to explore antimicrobial agents isolated from an endophytic fungus of Coleus amboinicus resulted in the finding of a potential aromatic compound having methoxy, hydroxyl, and methyl groups produced by Athelia rolfsii. This compound exhibited antibacterial activities with IC₅₀ values of <2 μg/mL against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Streptococcus mutans, and Pseudomonas aeruginosa. This study was aimed to determine the effect of varying fermentation conditions (types of media, carbon sources, nitrogen sources, temperature, and pH) on biomass, total metabolites, and bioactive compound production. Materials and Methods: The fungal cultures were subjected to various treatment conditions and incubated for 12 days at 25°C 160 rpm followed by analyzing the biomass, metabolite, and bioactive compound production. Results and Conclusion: The study found that although the maximum total metabolite production was achieved in the Tryptic Soy Broth medium, both biomass and bioactive compound production accumulated at the highest amount in Potato Dextrose Broth and Sabouraud Dextrose Broth media. Adding 1% of different types of carbon sources did not significantly enhance biomass, total metabolite, and bioactive compound production. Three types of organic nitrogen sources used in this study did not significantly affect biomass and total metabolite production, but adding peptone produced the highest amount of bioactive compound. Supplementing inorganic source of nitrogen to the culture medium decreased the production. While pH 5.5 was found to be the optimum condition for total metabolite production, pH 6–7 resulted in higher productivity of the bioactive compound. The total metabolite production was best produced at 25°C, whereas higher temperatures were needed to get optimum bioactive and biomass production. This study found that the total metabolite production was 7.8 times higher when the culture was grown in PDB medium supplemented with 1% sucrose and 1% peptone and incubated at 27°C at pH 6.5; whereas a 15% increase was observed in the bioactive compound production.

Background: Diazepam belongs to the benzodiazepine family of drugs and is mainly used for anxiety, muscle spasms, seizures, and insomnia. Long-term diazepam administration can cause genotoxicity, and oxidative stress is a likely molecular mechanism involved. Objectives: In this study, the benefits of melatonin against diazepam-induced oxidative damage and genotoxicity were investigated. Materials and Methods: Cultured peripheral lymphocytes were allocated to five groups: control, diazepam (100 μg/mL), melatonin (50 and 100 μM) with diazepam and cisplatin (0.05 μg/mL). After harvesting and preparing slides, the incidence of micronuclei (MN) was observed as a marker of genotoxicity. Then, in order to measure oxidative stress parameters, contents of glutathione (GSH) and lipid peroxidation (LPO) were determined. Results: Results documented increased MN and LPO and decrease in GSH levels in diazepam-administered lymphocytes versus those of the control group. When melatonin was given to diazepam-administered lymphocytes, they almost attenuated the increase of MN and LPO and restored the levels of GSH. Conclusion: Results showed that diazepam seems to induce genotoxicity in cultured human lymphocytes and oxidative stress plays an important role in it. Furthermore, it is concluded that melatonin efficiently protects against genotoxicity through its anti-oxidative effects.

Context: Mimusops elengi Linn. (Sapotaceae) is commonly known as bakul. Traditionally, the various parts of the plants have been used in the treatment of wound healing, pain, and tumor. Objective: To evaluate the role of Mimusops elengi extract (MEE) on proliferation, apoptosis, and bcl2 gene expression in Ehrlich ascites carcinoma (EAC) cells lines and establish the possible mechanisms linked with anticancer activity. Settings and Design: EAC cells were treated with methanol MEE (20–400 µg/mL) in time intervals of 24, 48, and 72 h. Materials and Methods: The antiproliferative effect of extract was evaluated using 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay; deoxyribonucleic acid (DNA) fragmentation study, cell cycle analysis, and Annexin V-fluorescein isothiocyanate (FITC) assay were performed to assess the apoptosis, and lastly, western blotting study was performed to assess the bands intensities using the ImageJ^® analysis (a Java-based image processing program system, National Institutes of Health and the Laboratory for Optical and Computational Instrumentation, University of Wisconsin, Madison, WI). Statistical Analysis Used: The data were analyzed using one-way analysis of variance followed by the Dunnett’s post hoc test. Results: MEE shows significant antiproliferative effect on EAC cell lines. In the DNA fragmentation assay, it shows significant fragmentation of DNA. In the cell cycle analysis and Annexin V-FITC assay, there was arrested in sub-G1 phase and initiation of cell apoptosis. In western blotting study, the extract shows low expression of bcl-2 and overexpression of Bax proteins. Conclusions: From the above result, it concludes that MEE has significant apoptosis-inducing properties.

Background: Opioid abuse prior to hospitalization in patients undergoing surgical procedures is associated with challenges in pain management, determining anesthetic dose, and providing nursing care. This study aimed to evaluate opioid abuse/dependence in hospitalized patients undergoing major elective surgery. Materials and Methods: A total of 1000 patients who were candidates for major elective surgery were assessed for demographic characteristics, perioperative and postoperative pain management, type and route of opioid abuse, and the current use of other abused substances. Results: Substance abuse was observed in 34% of surgical inpatients. The mean duration of substance abuse was 4.3 ± 1.9 years. Opioids were the most frequently abused substances (67.9%), followed by naswar (16.4%) and marijuana (8.5%). The inhalation route (60%) was the most common route for opioid use, followed by injection (29.4%) and oral route (10.6%). The prevalence of opioid abuse in females (54.6%) was significantly higher than males (45.4%), (P = 0.032, odd ratio =1.18, 95% CI = 1.03 -1.42). Low education level was associated with a higher rate of substance abuse (P = 0.042, Odd ratio=1.39, 95% CI = 1.14 -1.64), but there was no significant correlation between sex, education level, and substance abuse type. Overall, opioid abuse and dependence were associated with at least a 30% increase in the need for opioid analgesics to relieve postoperative pain. No opioid withdrawal signs were recorded in opioid-abusing patients. Conclusion: The results showed substance/drug abuse in more than one-third of surgical inpatients (34%) and a higher rate of drug abuse in women, which was an unexpected finding. Opioid abuse was significantly associated with education level. Opioid-dependent patients received higher doses of opioids during postoperative periods. Since opioid abuse can affect both preoperative and postoperative surgical and nursing health professionals, especially nurses, need continued medical education and professional support in caring for these individuals.

In Ayurveda, Talisapatradi choorna (TPC) and Vyoshadi choorna (VSC) are commonly used medicines for cough, cold, asthma, and rhinitis. These symptoms are due to upper respiratory infections of predominantly of viral origin. Currently, there are no effective medicines except indiscriminate uses of antibiotics, local anesthetics, and pain killers. The conventional formulation of TPC and VSC is difficult to administer so an easy manufacturing lozenge formulation was developed. The phytochemical analysis was done by preliminary thin layer chromatography (TLC) derivatization studies. High-performance thin layer chromatography (HPTLC) analysis confirmed the presence of herbal actives in the lozenge formulations. The TLC analysis results showed that TPC and VSC contain phytochemicals of flavonoids, steroids and phytosterols, and alkaloids family. The herbal actives were found to be stable in the final formulation without any interference with the excipients used in the formulation. The lozenges formulated from TPC and VSC are found to be promising alternatives to traditional form for the traditional Ayurvedic preparation. Compatibility study was done using Fourier transform infrared spectroscopy and HPTLC study.

Background: Chronic use of antidepressant drugs often results in drug-induced organ damage, which is mostly undetected and under-reported. The study aimed at evaluating the effect of selected antidepressants on organs and blood cell counts in adult albino rats. Materials and Methods: Adult rats were divided into four groups (n = 5): Group 1 (5 mL/kg of body weight/day normal saline), Group 2 (1 mg/kg of body weight/day risperidone), Group 3 (5 mg/kg of body weight/day fluoxetine), and Group 4 (15 mg/kg of body weight/day imipramine) for 14 days. The animals experienced different stressors during the treatment period to simulate physiological state of depression. On the 14th day, the animals were exposed to the forced swimming test 1 h after the respective treatments. On the 15th day, the animals were sacrificed under halothane anesthesia. Blood sample was collected. Liver and kidney were excised for histological examination. Results were analyzed using one-way analysis of variance. Results: Kidney histology was normal for all groups. Risperidone-exposed rats presented with hepatotoxicity with areas of zonal necrosis and partial central vein congestion. Neutrophil (%) was significantly reduced (P < 0.01) in all treatment groups when compared with controls. White blood cell count was significantly increased (P < 0.01) in the imipramine and risperidone treatment groups but significantly reduced (P < 0.01) in the fluoxetine treatment group when compared with controls. Also, the platelet count was significantly increased (P < 0.01) in the fluoxetine group but decreased in imipramine-and risperidone-treated groups. Conclusion: Chronic antidepressant use can cause changes in blood cell counts and drug-induced organ damage; hence, frequent organ function tests and blood count are required in patients undergoing chronic antidepressant therapy.

Background and Purpose: It has been shown that taking into account the polyvalence of action, tansy (Tanacetum vulgare L.) is a promising raw material for obtaining substances based on it as active pharmaceutical ingredients for the development of new potential herbal medicinal products. Materials and Methods: Ultrasound-assisted extraction (UAE) has been considered as one of the promising methods to optimize the technology of extracting biologically active substances (BAS) from T. vulgare flowers. Results: The advantages of the method, the mechanism of ultrasound action on plant cells, and the main factors affecting this process are indicated. Conclusion: The optimal technological parameters that allow the extraction of flavonoids calculated with reference to luteolin and hydroxycinnamic acids calculated with reference to chlorogenic acid in the maximum amount, namely, the raw material and extractant ratio, time, and the extraction frequency, have been determined. The high efficiency of UAE has been proven.

Background: Phenothiazine consists of a three-ring structure compound in which two benzene rings are connected with nitrogen and sulfur atoms at nonadjacent sides. Phenothiazine and its substituted derivatives are abundantly able to produce a variety of important pharmacological and valuable therapeutic effects, and till now, these are under profound investigational processes. Objective: To synthesize and evaluate the antihistaminic potential of some newly synthesized dinitrophenothiazine derivatives. Materials and Methods: Different derivatives have been synthesized by the appropriate chemical scheme using dinitrophenothiazine as a basic nucleus. The completion of the chemical reactions has been monitored by thin-layer chromatography. The chemical structures of the newly synthesized products (P1–P25) were affirmed by elemental analysis and by spectral (infra-red, ¹H nuclear magnetic resonance, and mass spectroscopy) findings and further examined for antihistaminic potential in guinea pigs. The synthesized products were also evaluated for their acute toxicity study and were found nontoxic. Results: The majority of the synthesized products of the dinitrophenothiazine series, namely, P07, P11, P12, P13, P15, P16, P17, P18, P19, and P20, have shown antihistaminic activity and compared with mepyramine (standard drug) at 0.8 µg/mL. Among the synthesized products, P18 was found to exhibit maximum antihistaminic activity. However, all the synthesized compounds were found to elicit a significant antihistaminic effect when compared with the standard drug. Conclusion: Therefore, dinitrophenothiazine compounds could be a good starting point to develop efficacious and potent analogues, as an antihistaminic agent in the treatment of allergic disorders.