Moringa oleifera and Its Biochemical Compounds: Potential Multi-targeted Therapeutic Agents Against COVID-19 and Associated Cancer Progression.

The Coronavirus disease-2019 (COVID-19) pandemic is a global concern, with updated pharmacological therapeutic strategies needed. Cancer patients have been found to be more susceptible to severe COVID-19 and death, and COVID-19 can also lead to cancer progression. Traditional medicinal plants have long been used as anti-infection and anti-inflammatory agents, and Moringa oleifera (M. oleifera) is one such plant containing natural products such as kaempferol, quercetin, and hesperetin, which can reduce inflammatory responses and complications associated with viral infections and multiple cancers. This review article explores the cellular and molecular mechanisms of action of M. oleifera as an anti-COVID-19 and anti-inflammatory agent, and its potential role in reducing the risk of cancer progression in cancer patients with COVID-19. The article discusses the ability of M. oleifera to modulate NF-κB, MAPK, mTOR, NLRP3 inflammasome, and other inflammatory pathways, as well as the polyphenols and flavonoids like quercetin and kaempferol, that contribute to its anti-inflammatory properties. Overall, this review highlights the potential therapeutic benefits of M. oleifera in addressing COVID-19 and associated cancer progression. However, further investigations are necessary to fully understand the cellular and molecular mechanisms of action of M. oleifera and its natural products as anti-inflammatory, anti-COVID-19, and anti-cancer strategies.

Investigating the effects of Thymus vulgaris essential oil, Allium cepa extract, and their active compounds (thymol and quercetin) on expression profile of genes related to Alzheimer's disease in PC12 model cell.

Thymus vulgaris and Allium cepa are plants with great medicinal importance. Thymol monoterpene and quercetin, which are present in these plants, have anti-Alzheimer's and antioxidant effects. The objectives of this research were investigating the effects of these compounds on the pathogenesis and progress of Alzheimer's disease in cells modeled by formaldehyde. MTT, flow cytometry, and RT-PCR were used to investigate the toxicity, survival rate and apoptosis of the cells, and the expression level of PP2A, GSK3, NMDAR, BACE1, and APP genes, respectively. Also, the total antioxidant capacity of the modeled cells was measured. The results showed that the two compounds as well as the plants extract and essential oil were able to increase the percentage of cell survival; among them, Thymus vulgaris essential oil had the greatest effect (93.55316 % in 48 h exposure). In addition, quercetin was able to reduce the rate of apoptosis in Alzheimer's cells (4.73 %) which was greater than the effects of other compounds. In general, the essential oil of Thymus vulgaris compared to thymol; and quercetin compared to Allium cepa extract showed more improving effects on the expression of genes involved in the disease. All four compounds increased the antioxidant capacity of the modeled cells compared to the control group, and these effects were almost equal between the compounds. According to the obtained results, both plants, especially Thymus vulgaris can be proposed as candidates to be included in the diet of Alzheimer's patients. In addition, polyphenols thymol and quercetin as derivates from the studied plants can be used in new drugs development for Alzheimer's disease, with greater safety than currently used drugs. These results are significant because most of the drug for Alzheimer's treatments such as cholinesterases (e.g. rivastigmine and donepezil) and memantine are chemically based and have many side effects.

Surface Modification of Poly(lactide-co-glycolide) Nanoparticles for the Sustained in vitro Release and the Enhanced Cytotoxicity of Chelidonine.

BACKGROUND: Chelidonine is a potent anticancer against several cell lines. However, low bioavailability and water solubility restrict the clinical applications of this compound. OBJECTIVE: The aim of this research was to develop a novel formulation of chelidonine encapsulated in the nanoparticles of poly(d l-lactic-co-glycolic acid) (PLGA) employing vitamin E D-α-tocopherol acid polyethylene glycol 1000 succinate (E TPGS) as a modifier to increase bioavailability. METHODS: Chelidonine-encapsulated PLGA nanoparticles were fabricated using a single emulsion method and modified by various concentrations of E TPGS. Nanoparticles were recognized in terms of morphology, surface charge, drug release, size, drug loading, and encapsulation efficiency to obtain the optimized formulation. The cytotoxicity of different nanoformulations in HT-29 cells was evaluated using the MTT assay. The cells were stained with propidium iodide and annexin V solution to evaluate apoptosis using flow cytometry. RESULTS: Spherical nanoparticles prepared with 2% (w/v) of E TPGS had the optimum formulation in the nanometer size range (153 ± 12.3 nm), with a surface charge of -14.06 ± 2.21 mV, encapsulation efficiency of 95.58 ± 3.47%, drug loading of 33.13 ± 0.19%, and drug release profile of 73.54 ± 2.33. In comparison with non-modified nanoparticles and free chelidonine, E TPGS-modified nanoformulations improved anti-cancer capability even after three-months storage. CONCLUSION: Our results showed that E TPGS is an effective biomaterial for surface modification of nanoparticles, which can serve as a potential treatment for cancer.

Identification of Leishmania species and frequency distribution of LRV1 and LRV2 viruses on cutaneous leishmaniasis patients in Isfahan Province, Iran.

PURPOSE: Leishmaniasis is one of the most serious health problems in developing countries. Iran is one of the endemic regions of cutaneous leishmaniasis. Leishmania RNA virus (LRV) is a dsRNA virus member of the Totiviridae family, which was first detected in the promastigotes of Leishmania braziliensis guyanensis. Our study aimed to investigate possible changes in the predominant and causative strains of CL and screening the LRV1 and LRV2 species genome from Leishmania species isolated from the lesions of patients. MATERIALS AND METHODS: Direct smear samples obtained from 62 patients with leishmaniasis referring to the Skin Diseases and Leishmaniasis Research Center in Isfahan province during 2021-2022 were examined. Total DNA extraction procedures and conservation of site-specific multiplex PCR and nested PCR were performed for detecting Leishmania species. The molecular identification of LRV1 and LRV2 viruses, samples were used for total RNA extraction and real-time (RT)-PCR analysis, followed by conducting a restriction enzyme assay to confirm the PCR products. RESULTS: Of the total Leishmania isolates, 54 and 8 isolates were identified as L. major and L. tropica, respectively. LRV2 was identified in 18 samples affected by L. major, while LRV1 was only detected in one of the samples with L. tropica. No LRV2 was found in any samples with L. tropica. The results showed that there was a significant relationship between LRV1 and the type of leishmaniasis (Sig. â€‹= â€‹0.009, P â€‹≤ â€‹0.05), while this relationship was not observed between LRV2 and the type of leishmaniasis. CONCLUSIONS: The presence of a significant number of LRV2 in isolated samples, as well as the recognition of LRV1 in one of the Old World leishmaniasis species, which is a new result, could pave the way for investigating further aspects of this disease and successful treatment strategies in future studies.

Effect of quercetin and Abelmoschus esculentus (L.) Moench on lipids metabolism and blood glucose through AMPK-α in diabetic rats (HFD/STZ).

Phosphoenolpyruvate carboxykinase (PEPCK) is a key enzyme in the glyconeogenesis pathway. The AMP-activated protein kinase alpha (AMPK-α) pathway regulates PEPCK, which itself is activated by the AMP/ATP ratio and liver kinase B1 (KB1). The Abelmoschus esculentus (L.) Moench (okra) plant contains a large amount of quercetin that can function as an agonist or an antagonist. The aim of this study was to examine the effects of quercetin flavonoid and A. esculentus extract on the level of AMPK-α expression and associated metabolic pathways. The findings demonstrate that metformin, quercetin, and okra extract may significantly raise AMPK-α levels while significantly lowering PEPCK and hormone-sensitive lipase (HSL) levels, in addition to improving glucose and lipid profiles. By stimulating KB1, these substances increased AMPK-α activation. Additionally, AMPK-α activation improved insulin resistance and Glucose transporter type 4 (GLUT4) gene expression levels. Since AMPK-α maintains energy balance and its activity has not been reported to be inhibited so far, it could be a potent therapeutic target. PRACTICAL APPLICATIONS: The development of effective AMPK-α agonists and antagonists holds promise for the treatment of metabolic disorders like diabetes. Dietary polyphenols are a valuable source for developing new drugs. However, due to the lack of understanding of the underlying mechanisms of their effect on cells, their use in the treatment of diabetes is controversial. In addition to chemicals that have medicinal benefits, chemists are searching for less harmful substances. Using plants containing bioactive chemicals for this purpose can be a good alternative to chemical drugs.

Iron oxide nanoparticles coated with polydopamine as a potential nano-photothermal agent for treatment of melanoma cancer: an in vivo study.

Melanoma is a metastatic cancer resistant to a wide range of therapies, including standard chemotherapy and radiation therapy, and cannot be treated with existing treatments owing to its intrinsic drug resistance. In terms of convenience and cheap cost of fabrication, one of the novel treatments is using polydopamine-coated iron oxide nanoparticles (IONs@PDA). Iron oxide nanoparticles (IONs) were synthesized (7.36 nm) and coated with polydopamine (15-20 nm). To examine the effect of photothermal ablation in melanoma cells (B16-F10), a Q-switched ruby laser (λ = 694 nm, spot size = 4 mm, output power = 5 J/s) was used. The prepared nanoprobe was applied to mice, and their survival after treatment was evaluated. Then histopathological studies were done on the livers and skins of the treated mice. The nanoparticles absorb the laser, raising the temperature and initiating photothermal treatment, with significant apoptosis (74%) after the 4th time of treatment. Photothermal therapy (PTT) by using IONs@PDA proved to be effective in the treatment of melanoma cells (tumor size of < 2 mm) without side effects. The lifespan of mice was significantly increased in a group of mice post-administered IONs@PDA and laser ablation. The fabricated nanoprobe (IONs@PDA) enhanced the melanoma cell apoptosis in the mice model, and it has promise for the treatment of melanoma (B16-F10) cells using photothermal therapy.

Comparison of the antisclerotic effect of hydroalcoholic extracts of Ocimum basilicum and Otostegia persica with quinacrine by inhibition of phospholipase A2 in male Wistar rats.

Objective: Hypercholesterolemia is now considered a major risk factor for development of atherosclerosis. The phospholipase A2 superfamily of enzymes has causal involvement in atherosclerosis. Atherosclerosis is one of the main causes of mortality in developed countries and in some developing countries such as Iran. The present study was designed to investigate the antihypercholesterolemic and antiatherogenic potentiality of ethanolic extracts of Ocimum basilicum (O. basilicum) and Otostegia persica (O. persica) in high-fat diet-induced hypercholesterolemic rats. Materials and Methods: In this study, 35 male rats were randomly divided into 1 normal diet and 4 high-fat diet groups. After two months of high-fat diet, measurement of cholesterol and LDL showed a significant difference between the groups. The 5 groups were as follows: Healthy rats receiving physiological serum, hypercholesterolemic rats without any treatment, hypercholesterolemic rats receiving quinacrine (30 mg/kg), hypercholesterolemic rats treated with extract of O. persica (300 mg/kg), and hypercholesterolemic rats treated with O. basilicum extract (300 mg/kg). Treatment was carried out for 40 days and finally, blood samples were collected and examined for cholesterol, triglyceride, high density lipoprotein, low density lipoprotein, C-reactive protein, phospholipase A2 , and interleukin-6 levels. Results: Treatment of hypercholesterolemic rats with ethanolic extracts of O. persica and O. basilicum did not cause significant changes in cholesterol, triglyceride and LDL or HDL levels. They caused a significant decrease in the levels of inflammatory factors of IL-6, PLA2 and CRP (p <0.05). Conclusion: Ethanolic extracts of O. persica and O. basilicum have antisclerotic effects by reducing the inflammatory factors and PLA2 activity.

Abelmoschus esculentus (L.) Moench improved blood glucose, lipid, and down-regulated PPAR-α, PTP1B genes expression in diabetic rats.

Okra (Abelmoschus esculentus (L.) Moench) is one of the most important medicinal plants for the treatment of diabetes. Flavonoids are one of the most significant components of okra and are responsible for their antioxidant, anti-inflammatory, and anti-diabetic effects. The aim of this research was to investigate the effect of okra extract on biochemical parameters and expression of protein tyrosine phosphatase 1B (PTP1B) and Peroxisome proliferator-activated receptors (PPARs) genes in a model of streptozotocin-induced diabetic male Wistar rat. Rats were given oral dosages of okra extract, (75% ethanolic extract) (200-400 mg/kg) for eight weeks. Our findings indicate that okra extract and quercetin therapy may lower blood glucose (BS), insulin, Triglyceride (TG), Cholesterol (Cho), and glucose transporter protein type-4 (GLUT4) levels. PTP1B and Peroxisome proliferator-activated receptor alpha (PPAR-α), which are important regulators of glucose and lipid homeostasis, are similarly inhibited by okra extract. According to the findings, okra extract also has antioxidant properties. Our results support the anti-hyperglycemic and hypolipidemic properties of okra extract. As a result, it appears to play a crucial role in controlling diabetes. PRACTICAL APPLICATIONS: In this paper, we show that flavonoids in okra may help diabetes by inhibiting the PTP1B and PPAR-pathways. This is significant because little research has been done on the impact of flavonoid chemicals in A. esculentus on the expression of PTP1B and PPAR using traditional methods of diabetes treatment. Many of today's essential drugs (e.g., atropine, ephedrine, tubocurarine, digoxin, and reserpine) have been developed by studding traditional treatments. Plant-derived medications are still used as a prototype by chemists in an effort to develop more effective and less risky treatments (e.g., morphine, taxol, physostigmine, quinidine, and emetine.

Efficacious antibacterial potency of novel bacteriophages against ESBL-producing Klebsiella pneumoniae isolated from burn wound infections.

BACKGROUND AND OBJECTIVES: Prevalence of extended spectrum ß-lactamase (ESBL) leads to the development of antibiotic resistance and mortality in burn patients. One of the alternative strategies for controlling ESBL bacterial infections is clinical trials of bacteriophage therapy. The aim of this study was to isolate and characterize specific bacteriophages against ESBL-producing Klebsiella pneumoniae in patients with burn ulcers. MATERIALS AND METHODS: Clinical samples were isolated from the hospitalized patient in burn medical centers, Iran. Biochemical screenings and 16S rRNA gene sequencing were determined. The phages were isolated from municipal sewerage treatment plants, Isfahan, Iran. TEM and FESEM, adsorption velocity, growth curve, host range, and the viability of the phage particles as well as proteomics and enzyme digestion patterns were examined. RESULTS: The results showed that Klebsiella pneumoniae Iaufa_lad2 (GenBank accession number: MW836954) was confirmed as an ESBL-producing strain using combined disk method. This bacterium showed significant sensitivity to three phages including PɸBw-Kp1, PɸBw-Kp2, and PɸBw-Kp3. Morphological characterization demonstrated that the phage PɸBw-Kp3 to the Siphoviridae family (lambda-like phages) and both phages PɸBw-Kp1 and ɸBw-Kp2 to the Podoviridae family (T1-like phages). The isolated bacteriophages had a large burst size, thermal and pH viability and efficient adsorption rate to the host cells. CONCLUSION: In present study, the efficacy of bacteriophages against ESBL pathogenic bacterium promises a remarkable achievement for phage therapy. It seems that, these isolated bacteriophages, in the form of phage cocktails, had a strong antibacterial impacts and a broad-spectrum strategy against ESBL-producing Klebsiella pneumoniae isolated from burn ulcers.

Bacteriophages PɸEn-CL and PɸEn-HO can eliminate MDR Enterobacter cloacae and Enterobacter hormaechei isolated from burn wound infections without toxicity for human skin cells.

The prevalence of multidrug-resistant (MDR) strains has caused serious problems in the treatment of burn infections. MDR Enterobactercloacae and Enterobacterhormaechei have been defined as the causative agents of nosocomial infections in burn patients. In this situation, examination of phages side effects on human cell lines before any investigation on human or animal that can provide beneficial information about the safety of isolated phages. The aim of this study was to isolate and identify the specific bacteriophages on MDR E. cloacae and E. hormaechei isolated from burn wounds and to analyze the efficacy, cell viability and cell cytotoxicity of phages on A-375 and HFSF-PI cell lines by MTT (3-(4, 5-dimethylthiazol-2-yl)2,5-diphenyl-tetrazolium bromide) colorimetric assay and lactate dehydrogenase (LDH) release assay. Phages were isolated from urban sewage Isfahan, Iran. Enterobactercloacae strain Iau-EC100 (GenBank accession number: MZ314381) and E. hormaechei strain Iau-EHO100 (GenBank accession number: MZ348826) were sensitive to the isolated phages. Transmission electron microscopy (TEM) results revealed that PɸEn-CL and PɸEn-HO that were described had the morphologies of Myovirus and Inovirus, respectively. Overall, MTT and LDH assays showed moderate to excellent correlation in the evaluation of cytotoxicity of isolated phages. The results of MTT and LDH assays showed that, phages PɸEn-CL and PɸEn-HO had no significant toxicity effect on A375 and HFSF-PI 3 cells. Phage PɸEn-HO had a better efficacy on the two tested cell lines than other phage. Our results indicated that, there were significant differences between the two cytotoxicity assays in phage treatment compared to control.

Isolation, characterization, and effectiveness of bacteriophage Pɸ-Bw-Ab against XDR Acinetobacter baumannii isolated from nosocomial burn wound infection.

OBJECTIVES: With emergence of drug resistance, novel approaches such as phage therapy for treatment of bacterial infections have received significant attention. The purpose of this study was to isolate and identify effective bacteriophages on extremely drug-resistant (XDR) bacteria isolated from burn wounds. MATERIALS AND METHODS: Pathogenic bacteria were isolated from hospitalized patient wounds in specialized burn hospitals in Iran, and their identification was performed based on biochemical testing and sequencing of the gene encoding 16S rRNA. Bacteriophages were isolated from municipal sewage, Isfahan, Iran. The phage morphology was observed by TEM. After detection of the host range, adsorption rate, and one-step growth curve, the phage proteomics pattern and restriction enzyme digestion pattern were analyzed. RESULTS: All isolates of bacteria were highly resistant to antibiotics. Among isolates, Acinetobacter baumannii strain IAU_FAL101 (GenBank accession number: MW845680), which was an XDR bacterium, showed significant sensitivity to phage Pɸ-Bw-Ab. TEM determined the phage belongs to Siphoviridae. They had double-stranded DNA. This phage showed the highest antibacterial effect at 15 °C and pH 7. Analysis of the restriction enzyme digestion pattern showed Pɸ-Bw-Ab phage was sensitive to most of the used enzymes and based on SDS-PAGE, protein profiles were revealed 43 to 90 kDa. CONCLUSION: Considering the potential ability of the isolated phage, it had an antibacterial impact on other used bacterial spp and also strong antibacterial effects on XDR A. baumannii. Also, it had long latency and low burst size. This phage can be a suitable candidate for phage therapy.

The Protective Effect of γ-aminobutyric Acid on Kidney Injury Induced by Renal Ischemia-reperfusion in Ovariectomized Estradiol-treated Rats.

BACKGROUND: Renal ischemia-reperfusion injury (IRI) is one of the most important causes of kidney injury, which is possibly gender-related. This study was designed to investigate the role of γ-aminobutyric acid (GABA) against IRI in ovariectomized estradiol-treated rats. METHODS: Thirty-five ovariectomized Wistar rats were used in six experimental groups. The first three groups did not subject to estradiol treatment and assigned as sham-operated, control, and GABA-treated groups. GABA (50 µmol/kg) and saline were injected in the treated and control groups 30 min before the surgery, respectively. The second three groups received the same treatments but received estradiol valerate (500 µg/kg, intramuscularly) 3 days prior to the surgery. The IRI was induced in the control and treated groups by clamping the renal artery for 45 min and then 24 h of reperfusion. All animals were sacrificed for the measurements. RESULTS: The serum levels of creatinine and blood urea nitrogen, kidney weight, and kidney tissue damage score significantly increased in the IRI rats (P < 0.05). GABA significantly decreased the aforementioned parameters (P < 0.05). The uterus weight increased significantly in rats that received estradiol (P < 0.05). Serum and kidney levels of nitrite (nitric oxide metabolite) did not alter significantly. Serum level of malondialdehyde increased significantly in the ovariectomized rats exposed to IRI (P < 0.05). CONCLUSIONS: It seems that GABA improved IRI in ovariectomized rats. Estradiol was also nephroprotective against IRI. However, co-administration of estradiol and GABA could not protect the kidney against IRI.

Effect of Γ-aminobutyric acid on kidney injury induced by renal ischemia-reperfusion in male and female rats: Gender-related difference.

BACKGROUND: The most important cause of kidney injury is renal ischemia/reperfusion injury (IRI), which is gender-related. This study was designed to investigate the protective role of Γ-aminobutyric acid (GABA (against IRI in male and female rats. MATERIALS AND METHODS: Thirty-six female and male wistar rats were assigned to six experimental groups. The IRI was induced by clamping renal vessels for 45 min then was performed reperfusion for 24 h. The group sex posed to IRI were pretreated with GABA and were compared with the control groups. RESULTS: Serum levels of creatinine and blood urea nitrogen, kidney weight, and kidney tissue damage score increased in the IRI alone groups, (P < 0.05), while GABA decreased these parameters in female significantly (P < 0.05), but not in male rats. Uterus weight decreased significantly in female rats treated with GABA. Testis weight did not alter in male rats. Serum level of nitrite and kidney level of malondialdehyde (MDA) had no significant change in both female and male rats. Kidney level of nitrite increased significantly in female rats experienced IRI and serum level of MDA increased significantly in males that were exposed to IRI (P < 0.05). CONCLUSION: GABA could ameliorate kidney injury induced by renal IRI in a gender dependent manner.

Effect of pomegranate flower extract on cisplatin-induced nephrotoxicity in rats.

BACKGROUND: Chemotherapy with cisplatin (CP) is accompanied with nephrotoxicity. OBJECTIVES: In the current study, pomegranate flower extract (PFE) has been evaluated as an antioxidant agent against CP-induced-renal toxicity. MATERIALS AND METHODS: Thirty two male Wistar rats were divided into five groups (6-8 in each group). The animals in groups 1 to 3 received PFE (25 mg/kg), PFE (50 mg/kg), and placebo (saline), respectively for 9 days, and onset of the day 3, they also received CP (2.5 mg/kg/day). Groups 4 and 5 were treated with PFE (25 and 50 mg/kg/day) for 9 days. Finally, the animals were sacrificed at day 9 after collecting blood samples. Kidneys were removed, weighted, and underwent histopathological investigation. RESULTS: The mean serum level of creatinine in group 3 (treated with CP and placebo) increased significantly (p<0.05), but the value decreased significantly (p<0.05) in group 1. Kidney weight in group 1 was lower than KW in groups 2 and 3, however it was significant when compared with group 2 (p<0.05). The serum nitrite level in group 2 was non-significantly lower than that in other groups, and no significant changes were observed in serum levels of malondialdehyde (MDA). Tissue level of nitrite was significantly decreased in the positive control and high dose of PFE plus CP-treated groups (p<0.05). Among CP-treated groups, low dose of PFE significantly improved kidney nitrite level (p<0.05). The results from histopathological staining indicated less tissue damage in group 1 when compared with group 3. CONCLUSIONS: It seems that low dose of PFE plays a protective role against CP-induced renal toxicity in rats.

Lithium carbonate inducing disorders in three parameters of rat sperm.

BACKGROUND: Lithium has a significant impact in reducing the symptoms of bipolar mania but in long periods of use with therapeutic doses can cause several disorders in various organs including the reproductive system. In this study, the effect of lithium on the sperm concentration and motility and forms of abnormal cells has been examined. MATERIALS AND METHODS: Male Wistar rats under the 48-day treatment with lithium carbonate at doses of 10, 20, and 30 mg/kg bw/day were kept in standard conditions. At the end of this period, sperm cells isolated from the cauda epididymis were counted, motility was estimated, and stained with smear papanicolaou stain. RESULTS: In lithium-treated groups, the rate of spermatogenesis and sperm quality were reduced and was seen in a dose-dependent manner. DISCUSSION: Lithium alters intracellular signaling pathways such as inositol phosphate metabolic cycle and cyclic adenosine mono phosphate (cAMP) system and adenosine triphosphate (ATP) synthesis. It also interferes in the division of sex cells to produce mature sperm and showed changes in the sperm cell membrane, function, and structure.