scholarly journals Mechanism of Anticancer Activity of Compounds Isolated from Two Species of Ziziphus (Z. jujube and Z. mauritiana)

2021 ◽  
pp. 170-183
Author(s):  
Sana Khurshid ◽  
Sana Javaid Awan ◽  
Ateeqa Naz ◽  
Safdar Hayat Khan ◽  
Saira Fiaz
Keyword(s):  
Anticancer Activity ◽  
Biological Properties ◽  
In Vivo Models ◽  
Calcium Phosphorus ◽  
Phosphorus Iron ◽  
Tumor Protein P53 ◽  
High Production ◽  
Underlying Mechanisms

Medicinal plants have been used to treat diseases for centuries. One group of such plants is Ziziphus species belonging to Rhamnaceae family. The extracts from plants of this genus has been found beneficial for the treatment of cancer caused by high production of reactive oxygen species resulting from different oxidative stress mediated conditions. The mechanism of anticancer activity of two different species of this plant (Z.jujube and Z.mauritiana) have been discussed in this review. The constituents of this plant include the flavonoids, triterpenes, potassium, calcium, phosphorus, iron, zinc, copper and polysaccharides such as reducing and non-reducing sugars. The underlying mechanisms of both species include the (Tumor protein P53) P53, (signal transducer and activator of transcription) STAT, (Matrix metalloproteinases) MMPs, (clustered regularly interspaced short palindromic repeats) CRISPR and flavonoids and triterpenic acid mechanisms. The effects of the extract on different cells lines in both in vitro and in vivo models have been studied by observing the induction of apoptosis and reduction in angiogenesis leading to reduction in progression and proliferation of cancer cell lines. The biological properties of Ziziphus include the anti-inflammatory, antioxidant, anticancer and hepato-protective characteristics.

scholarly journals Biological Properties of 6-Gingerol: A Brief Review

2014 ◽  
Vol 9 (7) ◽  
pp. 1934578X1400900 ◽  
Author(s):  
Shaopeng Wang ◽  
Caihua Zhang ◽  
Guang Yang ◽  
Yanzong Yang
Keyword(s):  
Fruits And Vegetables ◽  
Biological Activities ◽  
Zingiber Officinale ◽  
Biological Properties ◽  
Anticancer Activities ◽  
Inhibition Of Angiogenesis ◽  
Underlying Mechanisms ◽  
Pharmacologically Active

Numerous studies have revealed that regular consumption of certain fruits and vegetables can reduce the risk of many diseases. The rhizome of Zingiber officinale (ginger) is consumed worldwide as a spice and herbal medicine. It contains pungent phenolic substances collectively known as gingerols. 6-Gingerol is the major pharmacologically-active component of ginger. It is known to exhibit a variety of biological activities including anticancer, anti-inflammation, and anti-oxidation. 6-Gingerol has been found to possess anticancer activities via its effect on a variety of biological pathways involved in apoptosis, cell cycle regulation, cytotoxic activity, and inhibition of angiogenesis. Thus, due to its efficacy and regulation of multiple targets, as well as its safety for human use, 6-gingerol has received considerable interest as a potential therapeutic agent for the prevention and/or treatment of various diseases. Taken together, this review summarizes the various in vitro and in vivo pharmacological aspects of 6-gingerol and the underlying mechanisms.

scholarly journals α-Synuclein oligomers induce early axonal dysfunction in human iPSC-based models of synucleinopathies

2018 ◽  
Vol 115 (30) ◽  
pp. 7813-7818 ◽  
Author(s):  
Iryna Prots ◽  
Janina Grosch ◽  
Razvan-Marius Brazdis ◽  
Katrin Simmnacher ◽  
Vanesa Veber ◽  
...  
Keyword(s):  
Axonal Transport ◽  
Disease Patient ◽  
In Vivo Models ◽  
Human Neurons ◽  
Anterograde Axonal Transport ◽  
Axonal Dysfunction ◽  
Underlying Mechanisms ◽  
Human Ipsc

α-Synuclein (α-Syn) aggregation, proceeding from oligomers to fibrils, is one central hallmark of neurodegeneration in synucleinopathies. α-Syn oligomers are toxic by triggering neurodegenerative processes in in vitro and in vivo models. However, the precise contribution of α-Syn oligomers to neurite pathology in human neurons and the underlying mechanisms remain unclear. Here, we demonstrate the formation of oligomeric α-Syn intermediates and reduced axonal mitochondrial transport in human neurons derived from induced pluripotent stem cells (iPSC) from a Parkinson’s disease patient carrying an α-Syn gene duplication. We further show that increased levels of α-Syn oligomers disrupt axonal integrity in human neurons. We apply an α-Syn oligomerization model by expressing α-Syn oligomer-forming mutants (E46K and E57K) and wild-type α-Syn in human iPSC-derived neurons. Pronounced α-Syn oligomerization led to impaired anterograde axonal transport of mitochondria, which can be restored by the inhibition of α-Syn oligomer formation. Furthermore, α-Syn oligomers were associated with a subcellular relocation of transport-regulating proteins Miro1, KLC1, and Tau as well as reduced ATP levels, underlying axonal transport deficits. Consequently, reduced axonal density and structural synaptic degeneration were observed in human neurons in the presence of high levels of α-Syn oligomers. Together, increased dosage of α-Syn resulting in α-Syn oligomerization causes axonal transport disruption and energy deficits, leading to synapse loss in human neurons. This study identifies α-Syn oligomers as the critical species triggering early axonal dysfunction in synucleinopathies.

Advances on Quinazoline Based Congeners for Anticancer Potential

2021 ◽  
Vol 25 ◽  
Author(s):  
Parul Grover ◽  
Monika Bhardwaj ◽  
Garima Kapoor ◽  
Lovekesh Mehta ◽  
Roma Ghai ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Medicinal Chemistry ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Biological Properties ◽  
Anticancer Compounds ◽  
In Vivo Models ◽  
Appropriate Treatment

: The heterocyclic compounds have a great significance in medicinal chemistry because they have extensive biological activities. Cancer is globally the leading cause of death and it is a challenge to develop an appropriate treatment for the management of cancer. Continuous efforts are being made to find a suitable medicinal agent for cancer therapy. Nitrogen-containing heterocycles have received noteworthy attention due to their wide and distinctive pharmacological activities. One of the most important nitrogen-containing heterocycles in medicinal chemistry is ‘quinazoline’ that possesses a wide spectrum of biological properties. This scaffold is an important pharmacophore and is considered a privileged structure. The various substituted quinazolines displayed anticancer activity against different types of cancer. This review highlights the recent advances in quinazoline based molecules as anticancer agents. Several in-vitro and in-vivo models used along with the results are also included. A subpart briefing natural quinazoline containing anticancer compounds is also incorporated in the review.

scholarly journals Fracture Healing Research—Shift towards In Vitro Modeling?

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 748
Author(s):  
Moritz Pfeiffenberger ◽  
Alexandra Damerau ◽  
Annemarie Lang ◽  
Frank Buttgereit ◽  
Paula Hoff ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Ex Vivo ◽  
3D Models ◽  
In Vitro Models ◽  
Human Patient ◽  
In Vivo Models ◽  
Underlying Mechanisms ◽  
Biological Situation

Fractures are one of the most frequently occurring traumatic events worldwide. Approximately 10% of fractures lead to bone healing disorders, resulting in strain for affected patients and enormous costs for society. In order to shed light into underlying mechanisms of bone regeneration (habitual or disturbed), and to develop new therapeutic strategies, various in vivo, ex vivo and in vitro models can be applied. Undeniably, in vivo models include the systemic and biological situation. However, transferability towards the human patient along with ethical concerns regarding in vivo models have to be considered. Fostered by enormous technical improvements, such as bioreactors, on-a-chip-technologies and bone tissue engineering, sophisticated in vitro models are of rising interest. These models offer the possibility to use human cells from individual donors, complex cell systems and 3D models, therefore bridging the transferability gap, providing a platform for the introduction of personalized precision medicine and finally sparing animals. Facing diverse processes during fracture healing and thus various scientific opportunities, the reliability of results oftentimes depends on the choice of an appropriate model. Hence, we here focus on categorizing available models with respect to the requirements of the scientific approach.

scholarly journals Rhein Suppresses Colorectal Cancer Cell Growth by Inhibiting the mTOR Pathway In Vitro and In Vivo

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2176
Author(s):  
Haibo Zhang ◽  
Jun-Koo Yi ◽  
Hai Huang ◽  
Song Park ◽  
Sijun Park ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Migration ◽  
Cell Growth ◽  
Anticancer Activity ◽  
Migration And Invasion ◽  
Mtor Signaling Pathway ◽  
Underlying Mechanisms

Colorectal cancer (CRC) is one of the leading causes of mortality and morbidity in the world. Rhein has demonstrated therapeutic effects in various cancer models. However, its effects and underlying mechanisms of action in CRC remain poorly understood. We investigated the potential anticancer activity and underlying mechanisms of rhein in CRC in vitro and in vivo. Cell viability and anchorage-independent colony formation assays were performed to examine the antigrowth effects of rhein on CRC cells. Wound-healing and Transwell assays were conducted to assess cell migration and invasion capacity. Cell cycle and apoptosis were investigated by flow cytometry and verified by immunoblotting. A tissue microarray was used to detect mTOR expression in CRC patient tissues. Gene overexpression and knockdown were done to analyze the function of mTOR in CRC. The anticancer effect of rhein in vivo was assessed in a CRC xenograft mouse model. The results show that rhein significantly inhibited CRC cell growth by inducing S-phase cell cycle arrest and apoptosis. Rhein inhibited CRC cell migration and invasion through the epithelial–mesenchymal transition (EMT) process. mTOR was highly expressed in CRC cancer tissues and cells. Overexpression of mTOR promoted cell growth, migration, and invasion, whereas mTOR knockdown diminished these phenomena in CRC cells in vitro. In addition, rhein directly targeted mTOR and inhibited the mTOR signaling pathway in CRC cells. Rhein promoted mTOR degradation through the ubiquitin-proteasome pathway. Intraperitoneal administration of rhein inhibited HCT116 xenograft tumor growth through the mTOR pathway. In conclusion, rhein exerts anticancer activity in vitro and in vivo by targeting mTOR and inhibiting the mTOR signaling pathway in CRC. Our results indicate that rhein is a potent anticancer agent that may be useful for the prevention and treatment of CRC.

scholarly journals In Vitro and In Vivo Anti-Inflammatory Effects of Polyphyllin VII through Downregulating MAPK and NF-κB Pathways

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 875 ◽  
Author(s):  
Chao Zhang ◽  
Chaoying Li ◽  
Xuejing Jia ◽  
Kai Wang ◽  
Yanbei Tu ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Raw264.7 Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Steroidal Saponin ◽  
In Vivo Models ◽  
Protein Levels ◽  
Anti Inflammatory ◽  
Underlying Mechanisms

Background: Polyphyllin VII (PP7), a steroidal saponin from Paris polyphylla, has been found to exert strong anticancer activity. Little is known about the anti-inflammatory property of PP7. In this study, the anti-inflammatory activity and its underlying mechanisms of PP7 were evaluated in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and in multiple animal models. Methods: The content of nitric oxide (NO) was determined by spectrophotometry. The levels of prostaglandin E2 (PGE2) and cytokines were measured by enzyme-linked immunosorbent assay (ELISA) assay. The mRNA expression of pro-inflammatory genes was determined by qPCR. The total and phosphorylated protein levels were examined by Western blotting. The in vivo anti-inflammatory activities were evaluated by using mouse and zebrafish models. Results: PP7 reduced the production of NO and PGE2 and the protein and mRNA expressions of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and enzymes (inducible NO synthase [iNOS], cyclooxygenase-2 [COX-2], and Matrix metalloproteinase-9 [MMP-9]) in LPS-induced RAW264.7 cells by suppressing the NF-κB and MAPKs pathways. Notably, PP7 markedly inhibited xylene-induced ear edema and cotton pellet-induced granuloma formation in mice and suppressed LPS and CuSO4-induced inflammation and toxicity in zebrafish embryos. Conclusion: This study demonstrates that PP7 exerts strong anti-inflammatory activities in multiple in vitro and in vivo models and suggests that PP7 is a potential novel therapeutic agent for inflammatory diseases.

scholarly journals Production and Characterization of Chitooligosaccharides: Evaluation of Acute Toxicity, Healing, and Anti-Inflammatory Actions

2021 ◽  
Vol 22 (19) ◽  
pp. 10631
Author(s):  
Rafael Caetano Lisbôa Castro de Andrade ◽  
Nathália Kelly de Araújo ◽  
Manoela Torres-Rêgo ◽  
Allanny Alves Furtado ◽  
Alessandra Daniele-Silva ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Wound Repair ◽  
Biological Properties ◽  
In Vivo Models ◽  
Fibroblast Migration ◽  
A Cell ◽  
Anti Inflammatory ◽  
Two Stages

The search for promising biomolecules such as chitooligosaccharides (COS) has increased due to the need for healing products that act efficiently, avoiding complications resulting from exacerbated inflammation. Therefore, this study aimed to produce COS in two stages of hydrolysis using chitosanases derived from Bacillus toyonensis. Additionally, this study aimed to structurally characterize the COS via mass spectrometry, to analyze their biocompatibility in acute toxicity models in vivo, to evaluate their healing action in a cell migration model in vitro, to analyze the anti-inflammatory activity in in vivo models of xylol-induced ear edema and zymosan-induced air pouch, and to assess the wound repair action in vivo. The structural characterization process pointed out the presence of hexamers. The in vitro and in vivo biocompatibility of COS was reaffirmed. The COS stimulated the fibroblast migration. In the in vivo inflammatory assays, COS showed an antiedematogenic response and significant reductions in leukocyte migration, cytokine release, and protein exudate. The COS healing effect in vivo was confirmed by the significant wound reduction after seven days of the experiment. These results indicated that the presence of hexamers influences the COS biological properties, which have potential uses in the pharmaceutical field due to their healing and anti-inflammatory action.

scholarly journals A Ruthenium(II) Complex Containing a Redox-Active Semiquinonate Ligand as Potential Chemotherapeutic Agent: From Synthesis to In Vivo Studies

2019 ◽  
Author(s):  
Anna Notaro ◽  
Angelo Frei ◽  
Riccardo Rubbiani ◽  
Marta Jakubaszek ◽  
Uttara Basu ◽  
...  
Keyword(s):  
Chemotherapeutic Agent ◽  
Biological Properties ◽  
In Vivo Studies ◽  
Drug Candidate ◽  
Paramagnetic Resonance ◽  
In Vivo Models ◽  
Drug Candidates ◽  
X Ray Crystallography

Chemotherapy remains one of the dominant treatments to cure cancer. However, due to the many inherent drawbacks, there is a surge for new chemotherapeutic drugs. More specifically, the discovery of new drug candidates able to overcome severe side effects, the occurrence of resistance and the inefficacy toward metastatic tumours is highly desirable. In this work, we designed a new chemotherapeutic drug candidate against cancer, namely [Ru(DIP)2(sq)]PF6 (Ru-sq) (DIP = 4,7-diphenyl-1,10-phenanthroline; sq = semiquinonate ligand). The aim was to combine the great potential expressed by Ru(II) polypyridyl complexes and the singular redox and biological properties associated to the catecholate moiety. Several pieces of experimental evidence (e.g., X-ray crystallography, electron paramagnetic resonance, electrochemistry) demonstrate that the semiquinonate is the preferred oxidation state of the dioxo ligand in this complex. The biological activity of Ru-sq was then scrutinised in vitro and in vivo, and the results highlight the tremendous potential of this complex as a chemotherapeutic agent against cancer. Ru-sq was notably found have a much higher cytotoxic activity than cisplatin on several cell lines (i.e. in the nanomolar range), and, contrary to cisplatin, to have mitochondrial disfunction as one of its modes of action. The multicellular targets of Ru-sq could potentially be the key to overcome one of the main drawbacks of cisplatin i.e. the occurrence of resistance. Moreover, Ru-sq exhibited impressing activity on Multi Cellular Tumour Spheroids (MCTS) model, leading to a growth inhibition of the tumour even 13 days after treatment (20 μM). Very importantly, using two different in vivo models, it could be demonstrated that this compound is extremely well-tolerated by mice and has a very promising activity, curing, in some cases, tumour-bearing mice.<br>

scholarly journals Curcumin Combination Chemotherapy: The Implication and Efficacy in Cancer

Molecules ◽  
2019 ◽  
Vol 24 (14) ◽  
pp. 2527 ◽  
Author(s):  
Bee Ling Tan ◽  
Mohd Esa Norhaizan
Keyword(s):  
Anticancer Activity ◽  
Molecular Mechanisms ◽  
Curcuma Longa ◽  
Adverse Outcomes ◽  
Chemotherapeutic Drugs ◽  
Biological Mechanisms ◽  
Pharmacological Activities ◽  
Underlying Mechanisms

Many chemotherapeutic drugs have been used for the treatment of cancer, for instance, doxorubicin, irinotecan, 5-fluorouracil, cisplatin, and paclitaxel. However, the effectiveness of chemotherapy is limited in cancer therapy due to drug resistance, therapeutic selectivity, and undesirable side effects. The combination of therapies with natural compounds is likely to increase the effectiveness of drug treatment as well as reduce the adverse outcomes. Curcumin, a polyphenolic isolated from Curcuma longa, belongs to the rhizome of Zingiberaceae plants. Studies from in vitro and in vivo revealed that curcumin exerts many pharmacological activities with less toxic effects. The biological mechanisms underlying the anticancer activity of co-treatment curcumin and chemotherapy are complex and worth to discuss further. Therefore, this review aimed to address the molecular mechanisms of combined curcumin and chemotherapy in the treatment of cancer. The anticancer activity of combined nanoformulation of curcumin and chemotherapy was also discussed in this study. Taken together, a better understanding of the implication and underlying mechanisms of action of combined curcumin and chemotherapy may provide a useful approach to combat cancer diseases.

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