Jundishapur Journal of Natural Pharmaceutical Products
Volume:18 Issue: 4, Nov 2023

Context: 

Ziziphora clinopodioides is a well-known aromatic and culinary species of the genus Ziziphora. It has been used in Iranian folk medicine for healing digestive issues and fever. Extensive studies have been published on the characterization of the essential oil of this aromatic plant and its related biological properties. This study aimed to review the chemical composition and biological properties of Z. clinopodioides essential oil.

Evidence Acquisition: 

The literature survey was performed using search engines Google Scholar, Scopus, and PubMed, with the search period spanning within 1990 to 2022.

The investigation of Z. clinopodioides essential oil composition revealed that oxygenated monoterpenoids, such as pulegone and related menthane-type structures, in addition to aromatic monoterpenoids, such as carvacrol and thymol, comprise the majority of Z. clinopodioides essential oil components. Due to the high monoterpenoid content, Z. clinopodioides essential oil possesses outstanding biological properties, including antibacterial, antifungal, and insecticidal activity.

Ziziphora clinopodioides essential oil could be considered a natural, rich source of bioactive monoterpenoids encompassing potent biological activities. Therefore, based on the reported properties, it seems that Z. clinopodioides essential oil potentially has widespread industrial applications.

Context: 

α-Glucosidase (AG) inhibitory peptides represent a promising new class of therapeutic agents for the treatment of diabetes. However, there is a need to further understand the mechanisms and properties of these peptides.

Evidence Acquisition: 

In this comprehensive review, AG inhibitory peptides were categorized into three groups based on their length: short, medium, and long peptides. Data from the BioPEP-UWM database and recent publications were gathered to conduct a structure-activity relationship analysis for these peptides, focusing on identifying their reactive residues and AG binding sites.

 Through extensive examination, five substrate analogs (Trp376, Asp404, Ile441, Met519, and Phe649) and two catalytic residues (Asp518 and Asp616) were identified as the preferred inhibitory sites on AG. Furthermore, amino acid preferences and their positionings at different terminals on peptides, including the ultimate (N1 and C1), penultimate (N2 and C2), and antepenultimate (N3 and C3), were explored. Our findings revealed that these peptides were predominantly hydrophobic and tended to contain hydrophobic amino acids with hydrophobic alkyl/aryl side chains (such as lysine, glutamine, proline, and/or arginine). To gain further insights into peptide-AG interactions, docking analysis was performed, which highlighted the significance of hydrophobic bonds as the primary mode of interaction.

 By pooling all the findings, this review provided essential and practical information for the design and discovery of peptide-based anti-diabetic agents.

Zirconium (Zr) is known to be one of the metal compounds. Due to low toxicity, this compound is frequently used in biosensors, dentistry, and treatment of cancer. This review summarizes the studies conducted on Zr toxicity in vivo and in vitro. Overall, it has been concluded that Zr can be a poisonous component because it disrupts many different tissues and cells when exposed for an extended period of time. It has been observed that Zr induces oxidative stress in cells, resulting in cell death. These nanoparticles (NPs) have been shown to halt the cell cycle, breach various physiological barriers, and exert detrimental effects. As zirconium nanoparticle production is still under development, a standardized method has not been established. Consequently, the characteristics and functionality of these NPs may undergo alterations, potentially compromising their efficacy and safety.

Breast cancer is the second leading cause of death in women. The advent of machine learning (ML) has opened up a world of possibilities for the discovery and formulation of drugs. It is an exciting development that could revolutionize the pharmaceutical industry. By leveraging ML algorithms, researchers can now identify disease-related targets with greater accuracy. Additionally, ML techniques can be used to predict the toxicity and pharmacokinetics of potential drug candidates.

The main purpose of ML techniques, such as feature selection (FS) and classification, is to develop a learning model based on datasets.

This paper proposed a hybrid intelligent approach using a Binary Grey Wolf Optimization Algorithm and a Self-Organizing Fuzzy Logic Classifier (BGWO-SOF) for breast cancer diagnosis. The proposed FS approach can not only reduce the complexity of feature space but can also avoid overfitting and improve the learning process. The performance of this proposed approach was evaluated on the 10-fold cross-validation technique and the Wisconsin Diagnostic Breast Cancer dataset. Although the performance of breast cancer detection is highly dependent on classification accuracy, most good classification methods have an essential flaw in that they simply seek to maximize the accuracy of classification while ignoring the costs of misclassification among various categories. This is even more important in classification problems when the initial set of features is large. With such a large number of features, it is of special interest to search for a dependency between an optimal number of selected features and the accuracy of the classification model.

In experiments, standard performance evaluation metrics, including accuracy, F-measure, precision, sensitivity, and specificity, were performed. The evaluation resultsdemonstrated that theBGWO-SOFapproach achieves 99.70% accuracy and 99.66% F-measure, which outperforms other state-of-the-art methods.

During the comparison of the results, it was observed that the proposed approach gives better or more competitive results than other state-of-the-art methods. By leveraging the power of MLalgorithms and artificial intelligence (AI) and the findings of the current study, we can optimize the selection of natural pharmaceutical products for the treatment of breast cancer and maximize their efficacy.

Chemotherapy, the primary treatment for acute lymphoblastic leukemia (ALL), often yields inadequate responses. Epigallocatechin gallate (EGCG) has been shown to significantly affect tumor cells through various mechanisms, including cell cycle arrest, apoptosis, and autophagy.

The objective of this study is to explore the impact of EGCG on autophagy, apoptosis, and the interplay between them in NALM-6, a pre-B-ALL cell line.

NALM-6 cells were subjected to various concentrations of EGCG for 24 and 48 hours. Additionally, NH4Cl 10 mM was used as an autophagy inhibitor to examine this mechanism. The EGCG effect on cell viability and apoptosis was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), trypan blue exclusion assay, and flow cytometry. Moreover, western blot analysis and real-time PCR were performed to investigate autophagy.

Our findings demonstrated that EGCG significantly affected cell proliferation and viability. It reduced cell viability by 55.2 ± 8.4% (P < 0.0001) while inducing apoptosis by 51 ± 1.9% (P = 0.006). Furthermore, in the presence of NH4Cl, EGCG led to a 3.9 ± 1.8-fold increase in LC3 protein level (P = 0.001). It also resulted in an approximately 1.34 ± 0.34-fold enhancement in DRAM1 mRNA expression levels (P = 0.013), while reducing of LC3B by 33.3 ± 30.5% (P = 0.008), P62/SQSTM1 by 46.5 ± 28.3% (P < 0.001), and Atg2B by 45.5 ± 16.3% (P < 0.001). However, the inhibition of autophagy did not alter the apoptosis rate in either untreated or EGCG-treated cells.

Overall, our findings suggest that EGCG can trigger apoptosis and autophagy in NALM-6 cell line. However, blockage of autophagy does not appear to impact apoptosis in this cell line.

Gastrointestinal (GI) mucositis is one of the serious side effects of methotrexate (MTX) treatment. It is known that oxidative stress plays an important role in drug-induced side effects.

The present study aimed to assess the effect of gallic acid (GA) against MTX-induced intestinal mucositis in male Wistar rats.

Twenty-eight adult male Wistar rats were randomly divided into 4 groups (n = 7), including (1) control group; (2) GA group (gallic acid: 30 mg/kg/day, orally); (3) MTX group [20 mg/kg, intra peritoneal (IP)]; and (4) (MTX + GA) group (MTX: 20 mg/kg, IP and gallic acid: 30 mg/kg/day, orally). Then amounts of malondialdehyde (MDA), nitric oxide (NO), glutathione peroxidase (GPx), glutathione (GSH), superoxide dismutase (SOD), interleukin 2 (IL-2) and interleukin 6 (IL-6) were analyzed in serum samples and then the histopathological examinations of the duodenum and jejunum of animals groups.

The results showed that treatment with GA significantly reduced the MTX-induced elevation of serumMDA(P < 0.001), NO (P < 0.001), IL-2 (P < 0.001) and IL-6 (P < 0.001) contents and increased MTX-induced reduction in GSH (P < 0.001) content, GPx (P < 0.001) and SOD (P < 0.001) activity. In addition, the histopathological results showed that MTX leads to intestinal tissue damage, and gallic acid can remarkably improve the pathological changes.

Our results indicate that gallic acid can mitigate oxidative stress and pro-inflammatory parameters and also moderately prevent histopathological damage of the small intestine of rats exposed to MTX.

Polycystic ovary syndrome (PCOS) is an endocrine disorder affecting women. Previous research has shown that PCOS is associated with insulin resistance, oxidative stress, and immune system malfunctions. Also, the antioxidant effects of propolis and the positive effects of chitosan nanoparticles on the reproductive system have been demonstrated in some reports.

The current study is designed to investigate the protective effects of chitosan-propolis nanoparticle against estradiol valerate-induced (EV) PCOS model of rats compared to metformin (Met) (as a control treatment).

Intramuscular injection of EV (4 mg/kg, 28 days) was used to induce PCOS in rats, followed by oral administration of 500 mg/kg chitosan-propolis nanoparticle for 42 days. Rats were divided into 4 groups: Control, PCOS, metformin (PCOS and 150 mg/kg metformin), and chitosan-propolis nanoparticles (PCOS and chitosan-propolis nanoparticle administration, 500 mg/kg) groups.

All animals were subjected to serum factors analysis and histopathological study of ovaries. Estradiol valerate-induced induced PCOS while administration of chitosan-propolis nanoparticle recovered it. The body weight (P < 0.01) and ovarian morphology improved. The serum biochemical parameters, including estrogen (P < 0.05), progesterone (P < 0.001), vitamin D (P < 0.01), calcium (P < 0.01), and insulin resistance index (P < 0.05) were reversed after chitosan-propolis nanoparticle intervention. These EV-induced alterations included inhibited superoxide dismutase (SOD) activity (P < 0.05) and increased malondialdehyde (MDA) level (P< 0.001), and it was demonstrated that chitosan-propolis nanoparticle/Met administered for 42 consecutive days and gavages with EV reversed the oxidative stress factors. Additionally, in EV-treated animals, there was a significant upregulation of certain relativemRNAexpressions, such as monocyte chemoattractant protein (MCP) (P< 0.01), interleukin 18 (IL-18) (P< 0.05), and C-reactive protein (CRP) (P < 0.01) genes. These data clearly show that chitosan-propolis nanoparticle/Met may have a protective effect on this inflammatory disorder.

Taken together, the final results of this study are consistent with the assumption that chitosan-propolis nanoparticle /Met had ameliorative and protective effects against the harmful effects of EV. Although it is hypothesized that ameliorative effects might have been involved, the fundamental pathways remain to be illuminated.

Methotrexate (MTX), a folate antagonist used to treat cancer and inflammatory diseases, isknownto generate reactive oxygen species.

The research investigates the impact of dimethyl fumarate (DMF), a nuclear factor erythroid 2-related factor 2 (Nrf2) activator, on an MTX-induced mouse hepatotoxicity model.

Forty-two mice were divided into 6 groups: control, MTX, DMF 120, and 3 groups of MTX co-treated with DMF 30, 60, and 120 mg/kg. Dimethyl fumarate was gavaged once daily for 10 days. On the fifth day, the animals received MTX 20 mg/kg intraperitoneally. On the eleventh day, the animals were sacrificed, and serum and liver samples were collected to assess the level of oxidative/anti-oxidative and apoptotic/anti-apoptotic markers.

Dimethyl fumarate prevented the increase of liver function enzymes, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) induced by MTX (P < 0.001). It prevented the increase in AST and ALT levels, indicating liver recovery (P < 0.001). Furthermore, DMF restored antioxidant markers superoxide dismutase, catalase, glutathione peroxidase, and total thiol while reducing the level of thiobarbituric acid reactive substances (P < 0.001). Dimethyl fumarate also downregulated hepatic mRNA expression of caspase 3 and upregulated Bcl-2, heme oxygenase 1, and Nrf2 genes in MTX co-treated DMF groups.

Dimethyl fumarate alleviates oxidative stress and apoptosis, which may be achieved by the Nrf2/HO-1 pathway. Therefore, DMF may be clinically effective in preventing or treating MTX-induced hepatotoxicity.

Caffeine is an edible chemical compound obtained from various plants, such as tea and coffee. Caffeine is an alkaloid that is highly hydrophilic and has limited skin permeability. The lipophilic nature of the stratum corneum is a major barrier to the passage of this substance through the skin. Topical drug delivery systems can effectively transfer caffeine to the skin.

This study investigated the effect of pretreatment time with chemical enhancers on caffeine’s skin permeation.

The skin was subjected to additives such as sodium lauryl sulfate, sodium lauryl ethyl sulfate, tynoline, nanoxinol, and lecithin for 5, 15, and 30 minutes. Then, the parameters of caffeine permeability and structural changes in the skin due to additive adsorption were studied using Fourier Transform Infrared (FT-IR) spectrometry.

The enhancers increased the permeation of caffeine through the skin. There are different mechanisms for penetration enhancers, including lipid liquefaction, disruption of lipid bilayers, and irreversible denaturation of intracellular keratin.

Sodium lauryl sulfate can affect the skin permeability of caffeine.

Herbal medicines can be used as a possible therapeutic agent in inflammatory diseases.

This study aimed to determine the effect of Artemisia vulgaris (AV) hydro-alcoholic extract on oxidative stress and inflammatory damage in an experimental rat model of colitis.

Thirty male Sprague-Dawley rats were randomly divided into 6 groups: Control, colitis, sulfasalazine, AV50, AV100, and AV200. The animals of the AV groups were treated with the hydro-alcoholic extract of A. vulgaris via gavage for 72 h. Body weight was measured at the beginning and end of the experiment. In the end, serum levels of malondialdehyde (MDA) as a lipid peroxidation marker, antioxidants such as glutathione (GSH), superoxide dismutase (SOD) activity, serum tumor necrosis factor- (TNF-), and nitric oxide (NO) levels as inflammatory biomarkers were measured. Macroscopic and microscopic damage in the rat’s colon was also examined in histological studies.

The A. vulgaris extract treatment dose-dependently improved colonic injury (P < 0.001 to P < 0.05) and body weight (P < 0.001) in colitis rats. Moreover, it enhanced SOD activity and GSH levels (P < 0.001) and reduced serum MDA, TNF-, and NO levels (P < 0.001 to P < 0.01) in the rats with colitis.

Treatment with A. vulgaris could mitigate ulcerative colitis (UC) symptoms, which is probably attributed to its antioxidant and anti-inflammatory properties.

Research shows that -Pinene interacts with the opioidergic system.

This study aims to examine the toxicity and the effects of -Pinene on morphine tolerance and dependence in mice.

Guidelines No. 423 and No. 407 were used to investigate acute and sub-chronic toxicity, respectively. For sub-chronic toxicity analysis, the animals were sacrificed on day 28, and blood and tissue samples were collected. After inducing morphine tolerance or dependence, in both phases, animals received i.p. vehicle, diazepam(5 mg/kg), and-Pinene (3.125, 6.25, and12.5 mg/kg). Withdrawal signs were recorded for 30 minutes.

Only the acute dose of -Pinene showed mortality in animals, but mild lesions were seen in the brain, liver, and kidneys in the mice receiving its subchronic dose. Moreover, ALT, AST, ALP, and TG levels increased (P < 0.05) in female mice. Besides, 6.25 and 12.5 mg/kg (P < 0.001) of -Pinene and only its high dose (12.5 mg/kg) (P < 0.001) reduced the number of jumps in the tolerance and dependence phases, respectively. Diarrhea (P < 0.001), writhing (P < 0.001), rearing, and climbing (P < 0.05 and P < 0.001, respectively) behaviors decreased in the tolerance phase, and grooming, climbing, and teeth chattering declined in the dependence phase (P < 0.001).

The LD50 of -Pinene was lower than 2000 mg/kg, but its subchronic dose caused mild tissue toxicities and biochemical changes. Moreover,-Pinene decreased morphine tolerance and dependence and possibly was useful for the treatment of opioid dependence after complimentary trials.

As the repair capacity of the nervous system is low, stem cell therapy is a trend for replacement therapy. Dental pulp stem cells (DPSCs) have the potential to differentiate into many tissues, such as neurons. Harmine (7-methoxy-1methyl-9H-pyrido[3,4-b] indole) is an alkaloidal component of medicinal plants with a long history in traditional medicine. Alginate is a biocompatible hydrogel widely used as a biomaterial base in various scaffolds.

This study investigated whether harmine and encapsulation of cells in alginate hydrogel could improve DPSCs differentiation into neural cells.

DPSCs were cultured under standard stem cell culture conditions, then encapsulated in alginate hydrogel, and treated with differentiation medium with and without harmine. After 14 days, cell proliferation and differentiation were assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, real-time polymerase chain reaction (RT-PCR), and flow cytometry.

Harmine (5 and 10 M) significantly increased the proliferation and viability of DPSCs compared to the control group in both two-dimensional and three-dimensional culture systems (P < 0.05). The expression levels of three neural cell markers (nestin, microtubule-associated protein [MAP-2], and -tubulin III) in DPSCs-derived neural cells cultured in two-dimensional and three-dimensional culture systems were significantly increased in harmine-treated two-dimensionalandthree-dimensional culture systems compared to the control group (P < 0.05).

Either harmine or alginate hydrogel had an accelerating effect on DPSCs differentiation into neural cells. Harmine also increased the proliferation of the cells.