Tumoricidal properties of thymoquinone on human colorectal adenocarcinoma cells via the modulation of autophagy.

Colorectal cancer (CRC) is deadly anaplastic changes in the gastrointestinal tract with high-rate mortality. In recent years, the application of phytocompounds has been extended along with different therapeutic protocols. Here, we monitored the effects of Thymoquinone (TQ) on autophagy via mitochondrial function after modulation of the Wnt/ß-catenin signaling pathway.Human colorectal adenocarcinoma HT-29 cells were treated with TQ (60 µM) and 15 µM Wnt3a inhibitor (LGK974) for 48 h. The survival rate was evaluated using an MTT assay. The expression of Wnt-related factors (c-Myc, and Axin), angiogenesis (VE-Cadherin), and mitophagy-related factors (PINK1, OPTN) was assessed using real-time PCR assay. Protein levels of autophagy factors (Beclin-1, LC3, and P62) were monitored using western blotting. Using flow cytometry analysis, the intracellular accumulation of Rhodamine 123 was evaluated. The migration properties were analyzed using a scratch wound healing assay.Data indicated that TQ can reduce the viability of HT-29 cells compared to the control cells (p < 0.05). The expression of VE-Cadherin was inhibited while the expression of PINK1 was induced in treated cells (p < 0.05). Both LGK974 and TQ-treated cells exhibited activation of autophagy flux (Beclin-1↑, LC3II/I↑, and p62↓) compared to the control group (p < 0.05). TQ can increase intracellular accumulation of Rhodamine 123, indicating the inhibition of efflux mechanisms in cancer cells. Along with these changes, the migration of cells was also reduced (p < 0.05).TQ is a potential phytocompound to alter the dynamic growth of human colorectal HT-29 cells via the modulation of autophagy, and mitophagy-related mechanisms.

Cinnamic Acid Ameliorates Acetic Acid-induced Inflammatory Response through Inhibition of TLR-4 in Colitis Rat Model.

BACKGROUND: Cinnamic acid, an active compound in cinnamon spp., has anti-inflamatory and antioxidant characteristics and is favorable in managing inflammatory bowel diseases. OBJECTIVE: Evaluate cinnamic acid's effects on colitis in rats. METHODS: To induce colitis in experimental rats, excluding the sham group, a 4% intrarectal solution of acetic acid was administered. The rats were then given oral doses of cinnamic acid at 30, 45, and 90 mg/kg for two days. The animals were assessed for macroscopic and microscopic changes, and the levels of inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and myeloperoxidase (MPO) were measured using Eliza kits. Additionally, real-time PCR was performed to examine the gene level of toll-like receptor 4 (TLR-4) in the colon. RESULTS: Effective reduction of inflammation in acetic acid-induced colitis was achieved through cinnamic acid at doses of 45 and 90 mg/kg. The decrease was achieved by inhibiting the activities of TNF-α, IL-6, and MPO while downregulating the expression of TLR-4. It is important to note that macroscopic and microscopic evaluations were significant in determining the effectiveness of cinnamic acid in reducing inflammation. CONCLUSION: Downregulation of inflammatory cytokines and TLR-4 expression may contribute to cinnamic acid's anti-inflammatory effect.

Protective effect of a hydromethanolic extract from Fraxinus excelsior L. bark against a rat model of aluminum chloride-induced Alzheimer's disease: Relevance to its anti-inflammatory and antioxidant effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Fraxinus excelsior L. (FE), commonly known as the ash, belongs to the Oleaceae family and has shown several pharmacological and biological properties, such as antioxidant, immunomodulatory, neuroprotective, and anti-inflammatory effects. It has also attracted the most attention toward neuroinflammation. Moreover, FE bark and leaves have been used to treat neurological disorders, aging, neuropathic pain, urinary complaints, and articular pain in traditional and ethnomedicine. Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder resulting from the involvement of amyloid-beta, metal-induced oxidative stress, and neuroinflammation. AIM OF THE STUDY: The objective of the current study was to assess the neuroprotective effects of hydromethanolic extract from FE bark in an AlCl3-induced rat model of AD. MATERIALS AND METHODS: The maceration process was utilized to prepare the hydromethanolic extract of FE bark, and characterized by LC-MS/MS. To assess the anti-AD effects of the FE extract, rats were categorized into five different groups, AlCl3; normal control; FE-treated groups at 50, 100, and 200 mg/kg. Passive avoidance learning test, Y-maze, open field, and elevated plus maze behavioral tests were evaluated on days 7 and 14 to analyze the cognitive impairments. Zymography analysis, biochemical tests, and histopathological changes were also followed in different groups. RESULTS: LC-MS/MS analysis indicated the presence of coumarins, including isofraxidin7-O-diglucoside in the methanolic extract of FE as a new isofraxidin derivative in this genus. FE significantly improved memory and cognitive function, maintained weight, prevented neuronal damages, and preserved the hippocampus's histological features, as demonstrated by behavioral tests and histopathological analysis. FE increased anti-inflammatory MMP-2 activity, whereas it decreased that of inflammatory MMP-9. Moreover, FE increased plasma antioxidant capacity by enhancing CAT and GSH while decreasing nitrite levels in the serum of treated groups. In comparison between the treated groups, the rats that received high doses of the FE extract (200 mg/kg) showed the highest therapeutic effect. CONCLUSION: FE rich in coumarins could be an effective anti-AD adjunct agent, passing through antioxidant and anti-inflammatory pathways. These results encourage further studies for the development of this extract as a promising agent in preventing, managing, or treating AD and related diseases.

Lavender and metformin effectively propagate progesterone levels in patients with polycystic ovary syndrome: A randomized, double-blind clinical trial.

BACKGROUND: The present study aimed to evaluate the impacts of lavender and metformin on polycystic ovary syndrome (PCOS) patients. METHODS: We performed a randomized, double-blind clinical trial including 68 females aged 18 to 45, fulfilling the Rotterdam criteria for PCOS. The patients were randomized to receive lavender (250 mg twice daily) or metformin (500 mg three times a day) for 90 days. The serum progesterone was measured at baseline and after 90 days, one week before their expected menstruation. Moreover, the length of the menstrual cycle was documented. RESULTS: Our results showed that lavender and metformin treatment notably increased the progesterone levels in PCOS patients (increasing from 0.35 (0.66) and 0.8 (0.69) to 2.5 (6.2) and 2.74 (6.27) ng/mL, respectively, P < 0.001). However, we found no significant differences between the increasing effects of both treatments on progesterone levels. In addition, all patients in the lavender or metformin groups had baseline progesterone levels <3 ng/mL, reaching 14 (45.2%) patients >3 ng/mL. Lavender and metformin remarkably attenuated the menstrual cycle length in PCOS patients (decreasing from 56.0 (20.0) and 60 (12.0) to 42.0 (5.0) and 50.0 (14.0) days, respectively, P < 0.001). Furthermore, the decreasing effects of lavender on the menstrual cycle length were greater than the metformin group; however, it was not statistically significant (P = 0.06). CONCLUSION: Lavender effectively increased progesterone levels and regulated the menstrual cycles in PCOS patients, similar to metformin. Therefore, lavender may be a promising candidate for the treatment of PCOS.

Achillea wilhelmsii-Incorporated Chitosan@Eudragit Nanoparticles Intended for Enhanced Ulcerative Colitis Treatment.

Achillea wilhelmsii (A. wilhelmsii) contains several therapeutic phytochemicals, proposing a protective effect on inflammatory responses in autoimmune diseases such as ulcerative colitis (UC). However, its activities against UC encounter multiple obstacles. The current study aimed to formulate a colon-specific delivery of A. wilhelmsii for treating UC using chitosan nanoparticles (NPs) and Eudragit S100 as a mucoadhesive and pH-sensitive polymer, respectively. Core chitosan NP was loaded with A. wilhelmsii extract, followed by coating with Eudragit S100. Then, physicochemical characterizations of prepared NPs were conducted, and the anti-UC activity in the rat model was evaluated. The relevant physicochemical characterizations indicated the spherical NPs with an average particle size of 305 ± 34 nm and high encapsulation efficiency (88.6 ± 7.3%). The FTIR (Fourier transform infrared) analysis revealed the Eudragit coating and the extract loading, as well as the high radical scavenging ability of A. wilhelmsii was confirmed. The loaded NPs prevented the extract release in an acidic pH-mimicking medium and presented a complete release thereafter at a colonic pH. The loaded NPs markedly mitigated the induced UC lesions in rats, reflected by reducing inflammation, ulcer severity, and UC-related symptoms. Further, histopathological analysis exhibited reducing the extent of the inflammation and damage to colon tissue, and the determination of the involved pro-inflammatory cytokines in serum showed a significant reduction relative to free extract. The present results show that chitosan NPs containing A. wilhelmsii extract coated with Eudragit having proper physicochemical properties and substantial anti-inflammatory activity can significantly improve colonic lesions caused by UC.

Inhibiting Angiogenesis by Anti-Cancer Saponins: From Phytochemistry to Cellular Signaling Pathways.

Saponins are one of the broadest classes of high-molecular-weight natural compounds, consisting mainly of a non-polar moiety with 27 to 30 carbons and a polar moiety containing sugars attached to the sapogenin structure. Saponins are found in more than 100 plant families as well as found in marine organisms. Saponins have several therapeutic effects, including their administration in the treatment of various cancers. These compounds also reveal noteworthy anti-angiogenesis effects as one of the critical strategies for inhibiting cancer growth and metastasis. In this study, a comprehensive review is performed on electronic databases, including PubMed, Scopus, ScienceDirect, and ProQuest. Accordingly, the structural characteristics of triterpenoid/steroid saponins and their anti-cancer effects were highlighted, focusing on their anti-angiogenic effects and related mechanisms. Consequently, the anti-angiogenic effects of saponins, inhibiting the expression of genes related to vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1-α (HIF-1α) are two main anti-angiogenic mechanisms of triterpenoid and steroidal saponins. The inhibition of inflammatory signaling pathways that stimulate angiogenesis, such as pro-inflammatory cytokines, mitogen-activated protein kinase (MAPKs), and phosphoinositide 3-kinases/protein kinase B (PI3K/Akt), are other anti-angiogenic mechanisms of saponins. Furthermore, the anti-angiogenic and anti-cancer activity of saponins was closely related to the binding site of the sugar moiety, the type and number of their monosaccharide units, as well as the presence of some functional groups in their aglycone structure. Therefore, saponins are suitable candidates for cancer treatment by inhibiting angiogenesis, for which extensive pre-clinical and comprehensive clinical trial studies are recommended.

Anticancer Potential of Apigenin and Isovitexin with Focus on Oncogenic Metabolism in Cancer Stem Cells.

It has been demonstrated that cancer stem cells (CSCs) go through metabolic changes that differentiate them from non-CSCs. The altered metabolism of CSCs plays a vital role in tumor initiation, progression, immunosuppression, and resistance to conventional therapy. Therefore, defining the role of CSC metabolism in carcinogenesis has emerged as a main focus in cancer research. Two natural flavonoids, apigenin and isovitexin, have been shown to act synergistically with conventional chemotherapeutic drugs by sensitizing CSCs, ultimately leading to improved therapeutic efficacy. The aim of this study is to present a critical and broad evaluation of the anti-CSC capability of apigenin and isovitexin in different cancers as novel and untapped natural compounds for developing drugs. A thorough review of the included literature supports a strong association between anti-CSC activity and treatment with apigenin or isovitexin. Additionally, it has been shown that apigenin or isovitexin affected CSC metabolism and reduced CSCs through various mechanisms, including the suppression of the Wnt/ß-catenin signaling pathway, the inhibition of nuclear factor-κB protein expression, and the downregulation of the cell cycle via upregulation of p21 and cyclin-dependent kinases. The findings of this study demonstrate that apigenin and isovitexin are potent candidates for treating cancer due to their antagonistic effects on CSC metabolism.

Regulatory effects of trimetazidine in cardiac ischemia/reperfusion injury.

Ischemia/reperfusion (I/R) injury is a tissue damage during reperfusion after an ischemic condition. I/R injury is induced by pathological cases including stroke, myocardial infarction, circulatory arrest, sickle cell disease, acute kidney injury, trauma, and sleep apnea. It can lead to increased morbidity and mortality in the context of these processes. Mitochondrial dysfunction is one of the hallmarks of I/R insult, which is induced via reactive oxygen species (ROS) production, apoptosis, and autophagy. MicroRNAs (miRNAs, miRs) are non-coding RNAs that play a main regulatory role in gene expression. Recently, there are evidence, which miRNAs are the major modulators of cardiovascular diseases, especially myocardial I/R injury. Cardiovascular miRNAs, specifically miR-21, and probably miR-24 and miR-126 have protective effects on myocardial I/R injury. Trimetazidine (TMZ) is a new class of metabolic agents with an anti-ischemic activity. It has beneficial effects on chronic stable angina by suppressing mitochondrial permeability transition pore (mPTP) opening. The present review study addressed the different mechanistic effects of TMZ on cardiac I/R injury. Online databases including Scopus, PubMed, Web of Science, and Cochrane library were assessed for published studies between 1986 and 2021. TMZ, an antioxidant and metabolic agent, prevents the cardiac reperfusion injury by regulating AMP-activated protein kinase (AMPK), cystathionine-γ-lyase enzyme (CSE)/hydrogen sulfide (H2S), and miR-21. Therefore, TMZ protects the heart against I/R injury by inducing key regulators such as AMPK, CSE/H2S, and miR-21.

A systematic review on potential anticancer activities of Ficus carica L. with focus on cellular and molecular mechanisms.

BACKGROUND: Many substances derived from nutritional or medicinal plants have been studied for their chemopreventive and antineoplastic properties. Among those studied, Ficus carica has shown to have a significant ability to inhibit tumor formation and development of cancer cells through modulating various signaling mechanisms and interaction including a large number of cell signaling molecules. PURPOSE: The goal of this study is to provide a critical and complete evaluation of F. carica's anticancer capacity in various malignancies, as well as related molecular targets. METHODS: Research was conducted electronically on scholarly scientific databases, including Science Direct, PubMed, and Scopus. Published papers were analyzed and investigated using the keywords, Ficus carica, figs, cancer, malignancies and tumor based on established selection criteria. In this systematic review, 27 individual studies were considered. RESULTS: Treatment with F. carica alone or in combination with other medications was linked to anticancer activity with significant evidence. Furthermore, F. carica has been shown to use multitargeted pathways to prevent cancer initiation and development by modulating numerous dysregulated signaling cascades involved in cell proliferation, cell cycle regulation, apoptosis, autophagy inflammatory processes, metastasis, invasion, and angiogenesis. CONCLUSION: Our findings suggest that F. carica and its phytochemicals have the potential for cancer prevention and therapy. Nonetheless, additional mechanistic studies with pure compounds derived from F. carica and well-designed clinical trials are needed to advance our knowledge to clinical application.

Evaluation of the Cytotoxicity of Aqueous Extract and Oleo-Essential Oil of Dorema ammoniacum Plant Oleo-Gum Resin in Some Human Cancer Cell Lines.

Results: Aqueous extract and essential oil reduced the viability of A549 cancer cells in a concentration-dependent manner. The lowest inhibitory concentrations (IC50) for both samples of D. ammoniacum oleo-gum resin were 10 and 2.5 µg/ml for 24 hours in A549 cell line, respectively. After treatment with extract and essential oil of D. ammoniacum oleo-gum resin, ROS increased significantly compared to the control group. Although changes in caspase-3 did not show a significant increase in extract, the caspase-3 was found to be increased after exposure to essential oil and caspase-9 was downregulated after exposure to essential oil. Also, exposure to essential oil of D. ammoniacum caused a reduction in MMP level. Conclusion: Based on results, the cytotoxic effect of essential oil of D. ammoniacum can induce apoptosis toward A549 cell line via induction of oxidative stress, MMP depletion, and caspase-3 activation, which is independent to mitochondrial cytochrome c release and caspase-9 function.

Intrathecal administration of naringenin improves motor dysfunction and neuropathic pain following compression spinal cord injury in rats: relevance to its antioxidant and anti-inflammatory activities.

Background: Spinal cord injury (SCI) is one of the most debilitating disorders throughout the world, causing persistent sensory-motor dysfunction, with no effective treatment. Oxidative stress and inflammatory responses play key roles in the secondary phase of SCI. Naringenin (NAR) is a natural flavonoid with known anti-inflammatory and antioxidative properties. This study aims at evaluating the effects of intrathecal NAR administration on sensory-motor disability after SCI. Methods: Animals underwent a severe compression injury using an aneurysm clip. About 30 minutes after surgery, NAR was injected intrathecally at the doses of 5, 10, and 15 mM in 20 µL volumes. For the assessment of neuropathic pain and locomotor function, acetone drop, hot plate, inclined plane, and Basso, Beattie, Bresnahan tests were carried out weekly till day 28 post-SCI. Effects of NAR on matrix metalloproteinase (MMP)-2 and MMP-9 activity was appraised by gelatin zymography. Also, histopathological analyses and serum levels of glutathione (GSH), catalase and nitrite were measured in different groups. Results: NAR reduced neuropathic pain, improved locomotor function, and also attenuated SCI-induced weight loss weekly till day 28 post-SCI. Zymography analysis showed that NAR suppressed MMP-9 activity, whereas it increased that of MMP-2, indicating its anti-neuroinflammatory effects. Also, intrathecal NAR modified oxidative stress related markers GSH, catalase, and nitrite levels. Besides, the neuroprotective effect of NAR was corroborated through increased survival of sensory and motor neurons after SCI. Conclusions: These results suggest intrathecal NAR as a promising candidate for medical therapeutics for SCI-induced sensory and motor dysfunction.

Endothelial dysfunction and angiogenesis: what is missing from COVID-19 and cannabidiol story?

BACKGROUND: Among pathways involved in the pathogenesis of coronavirus disease 2019 (COVID-19), impaired endothelial cell (EC) function and angiogenesis have been discussed less frequently than others such as cytokine storm. These two do play parts in the development of various clinical manifestations of COVID-19 including acute respiratory distress syndrome (ARDS) and the hyper-coagulation state. METHODS: This narrative review attempts to gather recent data on the possible potential of cannabidiol in the treatment of COVID-19 with an eye on angiogenesis and endothelial dysfunction. Keywords including cannabidiol AND angiogenesis OR endothelial cell as well as coronavirus disease 2019 OR COVID-19 AND angiogenesis OR endothelial dysfunction were searched among the databases of PubMed and Scopus. RESULTS: Cannabidiol (CBD), as a therapeutic phytocannabinoid, has been approved by the Food and Drug Administration (FDA) for two types of seizures. Due to the potent anti-inflammatory properties of CBD, this compound has been suggested as a candidate treatment for COVID-19 in the literature. Although its potential effect on ECs dysfunction and pathologic angiogenesis in COVID-19 has been overlooked, other than cytokines like interleukin 1ß (IL-ß), IL-6, IL-8, and tumour necrosis factor α (TNFα) that are common in inflammation and angiogenesis, CBD could affect other important factors related to ECs function and angiogenesis. Data shows that CBD could decrease pathologic angiogenesis via decreasing ECs proliferation, migration, and tube formation. These activities are achieved through the suppression of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), urokinase plasminogen activator (uPA), matrix metalloproteinase 2 (MMP-2), MMP-9, intracellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1). Moreover, in an animal model, ARDS and sepsis responded well to CBD treatment. CONCLUSION: Altogether and considering the current use of CBD in the clinic, the conduction of further studies on CBD administration for patients with COVID-19 seems to be useful.

In vitro study of the mesenchymal stem cells-conditional media role in skin wound healing process: A systematic review.

Mesenchymal stromal cell (MSC)-conditioned medium (CM) offers a potential opportunity in the skin wound healing treatment. In this systematic review, an overview of the knowledge on this topic has been provided. A multistep search of the PubMed, Scopus and Science Direct database has been performed to identify papers on MSCs-conditional media used in skin wound healing. Eligibility checks were performed based upon predefined selection criteria. Of the 485 articles initially identified, consequently, only 96 articles apparently related to MSC-conditional media were initially assessed for eligibility. Finally, the 32 articles, strictly regarding the in vitro use of MSCs-conditional media in skin wounds, were analysed. The information analysed highlights the efficacy of MSCs-conditional media on skin wound healing in vitro models. The outcome of this review may be used to guide pre-clinical and clinical studies on the role of MSCs-conditional media in skin wound healing.

Natural products in the treatment of pulmonary emphysema: Therapeutic effects and mechanisms of action.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a class of lung diseases including chronic bronchitis, asthma, and emphysema. Long-time smoking is considered the main reason for developing emphysema. Emphysema can be defined as damage to the walls of the air sacs (alveoli) of the lung. It has been demonstrated that natural compounds with antioxidant and anti-inflammatory effects can effectively improve or protect the lung against this disease. This paper is dedicated to systematically review the effective natural compounds in the treatment of pulmonary emphysema. PURPOSE: This is the first systematic and comprehensive review on the role of plant-derived secondary metabolites in managing and/or treating pulmonary emphysema STUDY DESIGN AND METHODS: A systematic and comprehensive review was done based on Scopus, PubMed, and Cochrane Library databases were searched using the "emphysema", "plant", "herb", and "phytochemical" keywords. Non-English, review, and repetitive articles were excluded from the study. Search results were included in the Prisma diagram. RESULTS: From a total of 1285 results, finally, 22 articles were included in the present study. The results show that some herbs such as Scutellaria baicalensis Georgi and Monascus adlay and some phytochemicals such as gallic acid and quercetin and blackboard tree indole alkaloids affect more factors in improving the lung emphysema. Also, some natural compounds such as marijuana smoke and humic acid also play an aggravating role in this disease. It also seems that some of the medicinal plants such as PM014 herbal formula, pomegranate juice and açaí berry sometimes have side effects that are inconsistent with their therapeutic effects. CONCLUSION: We concluded that natural compounds can effectively improve pulmonary emphysema due to their antioxidant, anti-inflammatory, and anti-apoptotic properties. However, additional studies are suggested to prove efficacy and side effects.

Pediatric acute lymphoblastic leukemia management using multitargeting bioactive natural compounds: A systematic and critical review.

Pediatric acute lymphoblastic leukemia (pALL), a malignancy of the lymphoid line of blood cells, accounts for a large percentage of all childhood leukemia cases. Although the 5-year survival rate for children with ALL has greatly improved over years, using chemotherapeutics as its first-line treatment still causes short- and long-term side effects. Furthermore, induction of toxicity and resistance, as well as the high cost, limit their application. Phytochemicals, with remarkable cancer preventive and chemotherapeutic characteristics, may serve as old solutions to new challenges. Bioactive plant secondary metabolites have exhibited promising antileukemic and adjunctive effects by targeting various molecular processes, including autophagy, cell cycle, angiogenesis, and extrinsic/intrinsic apoptotic pathways. Although numerous reports have shown that various plant secondary metabolites can interfere with the progression of malignancies, including leukemia, there was no comprehensive review article on the effect of phytochemicals on pALL. This systematic review aims to provide critical and cohesive analysis of the potential of various naturally-occurring plant secondary metabolites in the management of pALL with the understanding of underlying molecular and cellular mechanisms of action.

Quercetin- and rutin-based nano-formulations for cancer treatment: A systematic review of improved efficacy and molecular mechanisms.

BACKGROUND: Natural products, with incredible chemical diversity, have been widely studied for their antitumor potential. Quercetin (QU) and quercetin glycoside (rutin), both polyphenolic flavonoids, stick out amongst the natural products, through various studies. Rutin (RU) and its aglycone (QU) have various biological properties that include antioxidant, anti-inflammatory, and anticarcinogenic activities. However, several side effects have restricted the efficacy of these polyphenolic flavonoids, which makes it necessary to use new strategies involving low and pharmacological doses of QU and RU, either alone or in combination with other anticancer drugs. PURPOSE: The aim of this study is to present a comprehensive and critical evaluation of the anticancer ability of different nano-formulations of RU and QU for improved treatment of various malignancies. METHODS: Studies were recognized via systematic searches of ScienceDirect, PubMed, and Scopus databases. Eligibility checks were conducted based upon predefined selection criteria. Ninety articles were included in this study. RESULTS: There was conclusive evidence for the association between anticancer activity and treatment with RU or QU. Furthermore, studies indicated that nano-formulations of RU and QU have greater anticancer activities in comparison to either agent alone, which leads to increased efficiency for treating cancer. CONCLUSION: The results of this systematic review demonstrate the anticancer activities of nano-formulations of RU and QU and their molecular mechanisms through preclinical studies. This paper also attempts to contribute to further research by addressing the current limitations/challenges and proposing additional studies to realize the full potential of RU- and QU-based formulations for cancer treatment.

Phytochemical and toxicological evaluation of Tamarix stricta Boiss.

The genus Tamarix includes several plant species well-known for their medicinal properties since ancient times. Tamarix stricta Boiss is a plant native to Iran which has not been previously investigated regarding its phytochemical and biological properties. This study assessed phytochemical and toxicological aspects of T. stricta. The plant was collected from Kerman province of Iran and after authentication by botanist, it was extracted with 70% ethanol. Total phenolic compounds, total flavonoids, and antioxidant properties were measured using spectrophometric methods. Quercetin content of the extract was measured after complete acid hydrolysis with high-performance liquid chromatography. The phytochemical profile of the extract was provided using liquid chromatography-mass spectrometry method. Acute toxicity study with a single intragastric dose of 5000 mg/kg of the extract and sub-chronic toxicity using 50, 100, and 250 mg/kg of the extract was assessed in Wistar rats. Phytochemical analysis showed that polyphenols constitute the major components of the extract. Also, the extract contained 1.552 ± 0.35 mg/g of quercetin. Biochemical, hematological, and histological evaluations showed no sign of toxicity in animals. Our experiment showed that T. stricta is a rich source of polyphenols and can be a safe medicinal plant. Further pharmacological evaluations are recommended to assess the therapeutic properties of this plant.

Garlic constituents for cancer prevention and therapy: From phytochemistry to novel formulations.

Garlic (Allium sativum L.) is one of the oldest plants cultivated for its dietary and medicinal values. This incredible plant is endowed with various pharmacological attributes, such as antimicrobial, antiarthritic, antithrombotic, antitumor, hypoglycemic, and hypolipidemic activities. Among the various beneficial pharmacological effects of garlic, the anticancer activity is presumably the most studied. The consumption of garlic provides strong protection against cancer risk. Taking into account the multi-targeted actions and absence of considerable toxicity, a few active metabolites of garlic are probably to play crucial roles in the killing of cancerous cells. Garlic contains several bioactive molecules with anticancer actions and these include diallyl trisulfide, allicin, diallyl disulfide, diallyl sulfide, and allyl mercaptan. The effects of various garlic-derived products, their phytoconstituents and nanoformulations have been evaluated against skin, prostate, ovarian, breast, gastric, colorectal, oral, liver, and pancreatic cancers. Garlic extract, its phytocompounds and their nanoformulations have been shown to inhibit the different stages of cancer, including initiation, promotion, and progression. Besides, these bioactive metabolites alter the peroxidation of lipid, activity of nitric oxide synthetase, nuclear factor-κB, epidermal growth factor receptor, and protein kinase C, cell cycle, and survival signaling. The current comprehensive review portrays the functions of garlic, its bioactive constituents and nanoformulations against several types of cancers and explores the possibility of developing these agents as anticancer pharmaceuticals.

Polyphenols and neurodegenerative diseases: focus on neuronal regeneration.

Neurodegenerative diseases are questions that modern therapeutics can still not answer. Great milestones have been achieved regarding liver, heart, skin, kidney and other types of organ transplantations but the greatest drawback is the adequate supply of these organs. Furthermore, there are still a few options available in the treatment of neurodegenerative diseases. With great advances in medical science, many health problems faced by humans have been solved, and their quality of life is improving. Moreover, diseases that were incurable in the past have now been fully cured. Still, the area of regenerative medicine, especially concerning neuronal regeneration, is in its infancy. Presently allopathic drugs, surgical procedures, organ transplantation, stem cell therapy forms the core of regenerative therapy. However, many times, the currently used therapies cannot completely cure damaged organs and neurodegenerative diseases. The current review focuses on the concepts of regeneration, hurdles faced in the path of regenerative therapy, neurodegenerative diseases and the idea of using peptides, cytokines, tissue engineering, genetic engineering, advanced stem cell therapy, and polyphenolic phytochemicals to cure damaged tissues and neurodegenerative diseases.

Structural modification of antineoplastic drug carmofur designed to the inhibition of SARS-CoV-2 main protease: A theoretical investigation.

A coherent account of the reaction mechanistic details, structural modifications, and inhibition potentials of antineoplastic drug carmofur and its modified analogs to inhibition of SARS-CoV-2 main protease (Mpro) is reported. The survey is performed by integrating the density functional based tight binding (DFTB3) with density functional theory (DFT) calculations. The inhibition process commences with nucleophilic attack from the sulfur atom on the carbonyl group, yielding a C-S bond formation, followed by a bond formation of the H-O9 by 2.07 Å, which results in a transition state contains a ring of six atoms. We found that although the direct addition of sulfhydryl group hydrogen to the N3 position is likely to happen, the proper position of the hydrogen to O9 decreases its accessibility. The thermodynamic stability of the complex was calculated to be highly sensitive to the substituent on the N11 position. Compounds with CH2NH2 and CH2F at N11 positions of carmofur revealed high thermodynamic stability to complexation with Mpro but induced no change in substrate-binding pocket comparable to carmofur. Replacing the N11 of carmofur with carbon (C-carmofur) was effective in terms of complexation stability at CH2CH2CH2F and CH2CH2CH2OH substitutions and occupation of S1 subsite by these structures in addition to the S2 subsite. Based on the resulted data, increasing the length of the carbon chain at introduced substitutions in N-carmofur almost decreases the complexation stability while in C-carmofur the trend is reversed. Throughout these information outputs, it was suggested that compounds d, e, i', and k' might be novel and more efficacious drug candidates instead of carmofur. We believe that our characterization of mechanistic details and structural modification on Mpro/carmofur complex will significantly intensify researchers' understanding of this system, and consequently help them to take advantage of results into practice and design various valuable derivatives for inhibition of SARS-CoV-2 main protease.