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.

Integrative Bioinformatics Analysis Reveals Potential Target Genes and PTEN Signaling in Breast Cancer and Effect of Zingiber officinale (Ginger) and Allium sativum (Garlic) extract on It.

INTRODUCTION: Breast cancer is the most common type of cancer in women. The construction of a competing gene network is an important step in the identification of the role of hub genes in breast cancers. In the current research, we used a number of bioinformatics tools to construct this network in breast cancer and investigated the combined effect of garlic and ginger on mice model of breast cancer. MATERIALS AND METHODS: We chose female mice weighing 18-20 g that were divided into 7 groups including; the cancer group receiving normal saline, different doses of ginger extract (100 and 500 mg/kg), different doses of garlic (50 and 100 mg/kg), tamoxifen (10 mg/ kg) and simultaneous garlic (100 mg/kg) and ginger (500 mg/kg) for 3 weeks intraperitoneal. Then we anesthetized the mice, isolated the tumor, and determined its size. Glutathione reductase and peroxidase levels and HER2, PTEN, and Cullin3 genes expression were measured. RESULTS: We identified 20 hub genes for breast cancer. In animal phase we found that tumor size in all mice receiving garlic and ginger showed a significant decrease compared to the control. Glutathione reductase showed a significant increase in all groups, especially in ginger 500 and combined groups. Glutathione peroxidase increased almost in all groups, especially in ginger 500. Expression of HER2 decreased in all treated groups. Expression of PTEN increased just in the combined group. CONCLUSION: Taken together, we introduce a number of novel promising diagnostic biomarkers for breast cancer. The use of garlic and ginger in the treatment of cancer can be useful. This action is probably through the antioxidant mechanism, and regulation of the expression of cancer related genes such as PTEN.

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.

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.

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.