Improving plant adaptation to soil antimony contamination: the synergistic contribution of arbuscular mycorrhizal fungus and olive mill waste.

BACKGROUND: This study aimed to investigate the alterations in biochemical and physiological responses of oat plants exposed to antimony (Sb) contamination in soil. Specifically, we evaluated the effectiveness of an arbuscular mycorrhizal fungus (AMF) and olive mill waste (OMW) in mitigating the effects of Sb contamination. The soil was treated with a commercial strain of AMF (Rhizophagus irregularis) and OMW (4% w/w) under two different levels of Sb (0 and 1500 mg kg-1 soil). RESULTS: The combined treatment (OMW + AMF) enhanced the photosynthetic rate (+ 40%) and chlorophyll a (+ 91%) and chlorophyll b (+ 50%) content under Sb condition, which in turn induced more biomass production (+ 67-78%) compared to the contaminated control plants. More photosynthesis in OMW + AMF-treated plants gives a route for phenylalanine amino acid synthesis (+ 69%), which is used as a precursor for the biosynthesis of secondary metabolites, including flavonoids (+ 110%), polyphenols (+ 26%), and anthocyanins (+ 63%) compared to control plants. More activation of phenylalanine ammonia-lyase (+ 38%) and chalcone synthase (+ 26%) enzymes in OMW + AMF-treated plants under Sb stress indicated the activation of phenylpropanoid pathways in antioxidant metabolites biosynthesis. There was also improved shifting of antioxidant enzyme activities in the ASC/GSH and catalytic pathways in plants in response to OMW + AMF and Sb contamination, remarkably reducing oxidative damage markers. CONCLUSIONS: While individual applications of OMW and AMF also demonstrated some degree of plant tolerance induction, the combined presence of AMF with OMW supplementation significantly enhanced plant biomass production and adaptability to oxidative stress induced by soil Sb contamination.

Production of Targeted Estrone Liposomes Using a Herringbone Micromixer.

Liposomes are spherical vesicles formed from bilayer lipid membranes that are extensively used in targeted drug delivery as nanocarriers to deliver therapeutic reagents to specific tissues and organs in the body. Recently, we have reported using estrone as an endogenous ligand on doxorubicin-encapsulating liposomes to target estrogen receptor (E.R.)-positive breast cancer cells. Estrone liposomes were synthesized using the thin-film hydration method, which is a long, arduous, and multistep process. Here, we report using a herringbone micromixer to synthesize estrone liposomes in a simple and rapid manner. A solvent stream containing the lipids was mixed with a stream of phosphate buffer saline (PBS) inside a microchannel integrated with herringbone-shaped ridges that enhanced the mixing of the two streams. The small scale involved enabled rapid solvent exchange and initiated the self-assembly of the lipids to form the required liposomes. The effect of different parameters on liposome size, such as the ratio between the flow rate of the solvent and the buffer solutions (FRR), total flow rate, lipid concentrations, and solvent type, were investigated. Using this commercially available chip, we obtained liposomes with a radius of 66.1 ± 11.2 nm (mean ± standard deviation) and a polydispersity of 22% in less than 15 minutes compared to a total of ~11 hours using conventional techniques. Calcein was encapsulated inside the prepared liposomes as a model drug and was released by applying ultrasound at different powers. The size of the prepared liposomes was stable over a period of one month. Overall, using microfluidics to synthesize Estrone-liposomes simplified the procedure considerably and improved the reproducibility of the resulting liposomes.

Isatin-based benzyloxybenzene derivatives as monoamine oxidase inhibitors with neuroprotective effect targeting neurogenerative disease treatment.

Eighteen isatin-based benzyloxybenzaldehyde derivatives from three subseries, ISB, ISFB, and ISBB, were synthesized and their ability to inhibit monoamine oxidase (MAO) was evaluated. The inhibitory activity of all synthesized compounds was found to be more profound against MAO-B than MAO-A. Compound ISB1 most potently inhibited MAO-B with an IC50 of 0.124 ± 0.007 µM, ensued by ISFB1 (IC50 = 0.135 ± 0.002 µM). Compound ISFB1 most potently inhibited MAO-A with an IC50 of 0.678 ± 0.006 µM, ensued by ISBB3 (IC50 = 0.731 ± 0.028 µM), and had the highest selectivity index (SI) value (55.03). The three sub-parental compounds, ISB1, ISFB1, and ISBB1, had higher MAO-B inhibition than the other derivatives, indicating that the substitutions of the 5-H in the A-ring of isatin diminished the inhibition of MAO-A and MAO-B. Among these, ISB1 (para-benzyloxy group in the B-ring) displayed more significant MAO-B inhibition when compared to ISBB1 (meta-benzyloxy group in the B-ring). ISB1 and ISFB1 were identified to be competitive and reversible MAO-B inhibitors, having Ki values of 0.055 ± 0.010, and 0.069 ± 0.025 µM, respectively. Furthermore, in the parallel artificial membrane penetration assay, ISB1 and ISFB1 traversed the blood-brain barrier in the in vitro condition. Additionally, the current study found that ISB1 decreased rotenone-induced cell death in SH-SY5Y neuroblastoma cells. In docking and simulation studies, the hydrogen bonding formed by the imino nitrogen in ISB1 and the pi-pi stacking interaction of the phenyl ring in isatin significantly aided in the protein-ligand complex's stability, effectively inhibiting MAO-B. According to these observations, the MAO-B inhibitors ISB1 and ISFB1 were potent, selective, and reversible, making them conceivable therapies for neurological diseases.

Cytotoxic and Antioxidant Potential of Launaea mucronata Forssk Essential Oil Growing in Northern Saudi Arabia.

Essential oils are naturally occurring multicomponent combinations of isoprenoids with distinctive odors that are produced by aromatic plants from mevalonic acid. They are extensively applied in aromatherapy for the treatment of various ailments. To investigate the potential therapeutic value of the ingredients in Launaea mucronata essential oil (EO), gas chromatography-mass spectrometry (GC-MS) analysis was used for essential oil characterization. Then, 2,2-diphenyl-1-picrylhydrazyl (DPPH), ß-carotene/linoleic acid, and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays were used to evaluate the antioxidants. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to estimate the cytotoxicity. Following a thorough analysis of the GC-MS chromatogram, 87 components representing 97.98% of the entire EO mixture were identified. N-eicosane (10.92%), 2E,6Z-farnesol (10.74%), and 2Z,6E-farnesyl acetone (46.35%) were determined to be the major components of the oil. When the produced EO was evaluated for its antioxidant properties, it showed a strong inhibitory effect (%) of 65.34 at a concentration of 80 µg/mL. The results (g/mL) showed a positive response against the tested cell lines for HCT-116, MCF-7, and HepG2 (8.45, 10.24, and 6.78 g/mL, respectively). A high-concentration mixture of deadly components consisting of farnesol, bisabolol, eicosane, and farnesyl acetone may be responsible for this significant cytotoxic action, which was especially noticeable in the HepG2 cell line. Molecular docking occurred between farnesol and farnesyl acetone with the target residues of topoisomerases I and II, CDK4/cyclD1, and Aurora B kinases; these showed binding free energies ranging from -4.5 to -7.4 kcal/mol, thus demonstrating their antiproliferative action. In addition, farnesol and farnesyl acetone fulfilled most of the ADME and drug-likeness properties, indicating their activity.

Hesperidin Attenuates Titanium Dioxide Nanoparticle-Induced Neurotoxicity in Rats by Regulating Nrf-2/TNF-α Signaling Pathway, the Suppression of Oxidative Stress, and Inflammation.

Background: Titanium dioxide nanoparticles (TiO2NPs) are widely utilized and consumed mainly as food additives. Oxidative stress is considered to be the basic effect of TiO2NPs through biological interactions. Hesperidin (HSP) is a bioflavonoid (flavanone glycoside) with lipid-lowering, inflammation, oxidative stress suppression, antihypertensive, cancer-fighting, and antiedema effects. Objective: This study was to investigate the possible protective influences of HSP of subchronic oral TiO2NP exposure on the brains of rats, including neurotransmitters, oxidative stress/antioxidant parameters, inflammatory markers, and histological changes in the brains of adult male albino rats. Methodology: The experiment was executed on 80 albino rats. The animals were randomly divided into 4 equal groups. The first group served as a control; the second group was treated with oral doses of HSP (100 mg/kg Bw daily); the third group received TiO2NPs (200 mg/kg Bw orally daily); and the fourth group was treated with TiO2NPs and an oral dose of HSP daily for 8 weeks. Blood samples were obtained for biochemical analysis. Neurotransmitters, oxidative stress biomarker levels, and inflammatory markers were measured in brain homogenates. Histological examination of the brain was performed through H&E staining. Results: Coadministration of hesperidin with TiO2NPs orally for 8 weeks decreased the levels of MDA, TNF-α, AChE, and dopamine in brain homogenates, which were increased in the TiO2NP group. It increased the other oxidative biomarkers (SOD, CAT, and GPx) and Nrf-2 expression levels. Brain histological sections of the TiO2NP-treated group show degeneration, necrosis, congestion, and inflammatory cell infiltration that decreased markedly in the coadministration of hesperidin with the TiO2NP group. Conclusion: Hesperidin cotreatment offers significant protection against TiO2NP-induced oxidative stress and biochemical and histological alteration in the brain.

A computational investigation of thymidylate synthase inhibitors through a combined approach of 3D-QSAR and pharmacophore modelling.

Thymidylate synthase (TS) is a crucial target of cancer drug discovery and is mainly involved in the De novo synthesis of the DNA precursor thymine. In the present study, to generate reliable models and identify a few promising molecules, we combined QSAR modelling with the pharmacophore hypothesis-generating technique. Input molecules were clustered on their similarity, and a cluster of 74 molecules with a pyrimidine moiety was chosen as the set for 3D-QSAR and pharmacophore modelling. Atom-based and field-based 3D-QSAR models were generated and statistically validated with R2 > 0.90 and Q2 > 0.75. The common pharmacophore hypothesis(CPH) generation identified the best six-point model ADHRRR. Using these best models, a library of FDA-approved drugs was screened for activity and filtered via molecular docking, ADME profiling, and molecular dynamics simulations. The top ten promising TS-inhibiting candidates were identified, and their chemical features profitable for TS inhibitors were explored.Communicated by Ramaswamy H. Sarma.

Piperidine: A Versatile Heterocyclic Ring for Developing Monoamine Oxidase Inhibitors.

The monoamine oxidase enzyme (MAO), which is bound on the membrane of mitochondria, catalyzes the oxidative deamination of endogenous and exogenous monoamines, including monoamine neurotransmitters such as serotonin, adrenaline, and dopamine. These enzymes have been proven to play a significant role in neurodegeneration; thus, they have recently been researched as prospective therapeutic targets for neurodegenerative illness treatment and management. MAO inhibitors have already been marketed as neurodegeneration illness treatments despite their substantial side effects. Hence, researchers are concentrating on developing novel molecules with selective and reversible inhibitory properties. Piperine, which is a phytochemical component present in black pepper, has been established as a potent MAO inhibitor. Piperine encompasses a piperidine nucleus with antibacterial, anti-inflammatory, antihypertensive, anticonvulsant, antimalarial, antiviral, and anticancer properties. The current Review focuses on the structural changes and structure-activity relationships of piperidine derivatives as MAO inhibitors.

Mitigation of acetaminophen-induced liver toxicity by the novel phosphatidylinositol 3-kinase inhibitor alpelisib.

The sterile inflammatory response mediated by Toll-like receptors (TLRs) 4 and 9 is implicated in the massive hepatic damage caused by acetaminophen (APAP)-overdose. There is a crosstalk between TLR-dependent signaling with other intracellular kinases like phosphatidylinositol 3-kinases (PI3Ks). Nevertheless, the detailed role of PI3Kα is still unknown in hepatic sterile inflammation. Accordingly, the effect of the novel PI3Kα inhibitor alpelisib was investigated in the setting of APAP-driven sterile inflammation in the liver. This was examined by pretreating mice with alpelisib (5 and 10 mg/kg, oral) 2 h before APAP (500 mg/kg, i.p.)-intoxication. The results indicated that alpelisib dose-dependently lowered APAP-induced escalation in serum liver function biomarkers and hepatic necroinflammation score. Alpelisib also attenuated APAP-induced rise in cleaved caspase 3 and proliferating cell nuclear antigen (PCNA) in the liver hepatocytes, as indices for apoptosis and proliferation. Mechanistically, inhibition of PI3Kα by alpelisib limited APAP-induced overproduction of the pro-inflammatory tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6 in the blood circulation via switching off the activation of several signal transduction proteins, including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), signal transducer and activator of transcription-3 (Stat-3), glycogen Synthase Kinase (GSK)-3ß and nuclear factor (NF)-κB. Alpelisib also impaired APAP-instigated immune cell infiltration in the liver via reducing systemic granulocyte/macrophage-colony stimulating factor (GM-CSF) release and reversed APAP-induced abnormalities in the systemic and hepatic levels of the anti-inflammatory IL-10 and IL-22. In conclusion, selective modulation of the PI3Kα activity by alpelisib can hinder the inflammatory response and infiltration of immune cells occurring by APAP-hepatotoxicity.

Assembling a Cinnamyl Pharmacophore in the C3-Position of Substituted Isatins via Microwave-Assisted Synthesis: Development of a New Class of Monoamine Oxidase-B Inhibitors for the Treatment of Parkinson's Disease.

Monoamine oxidase (MAO, EC 1.4.3.4) is responsible for the oxidative breakdown of both endogenous and exogenous amines and exists in MAO-A and MAO-B isomers. Eighteen indole-based phenylallylidene derivatives were synthesized via nucleophilic addition reactions comprising three sub-series, IHC, IHMC, and IHNC, and were developed and examined for their ability to inhibit MAO. Among them, compound IHC3 showed a strong MAO-B inhibitory effect with an IC50 (half-maximal inhibitory concentration) value of 1.672 µM, followed by IHC2 (IC50 = 16.934 µM). Additionally, IHC3 showed the highest selectivity index (SI) value of >23.92. The effectiveness of IHC3 was lower than the reference pargyline (0.14 µM); however, the SI value was higher than pargyline (17.16). Structurally, the IHC (-H in the B-ring) sub-series exhibited relatively stronger MAO-B inhibition than the others. In the IHC series, IHC3 (-F in the A-ring) exhibited stronger MAO-B suppression than the other substituted derivatives in the order -F > -Br > -Cl > -OCH3, -CH3, and -H at the 2-position in the A-ring. In the reversibility and enzyme kinetics experiments, IHC3 was a reversible inhibitor with a Ki value of 0.51 ± 0.15 µM for MAO-B. Further, it was observed that IHC3 greatly decreased the cell death caused by rotenone in SH-SY5Y neuroblastoma cells. A molecular docking study of the lead molecule was also performed to determine hypothetical interactions in the enzyme-binding cavity. These findings suggest that IHC3 is a strong, specific, and reversible MAO-B inhibitor that can be used to treat neurological diseases.

Synthesis, Characterization, and Biological Evaluation of Meldrum's Acid Derivatives: Dual Activity and Molecular Docking Study.

In the presented study, eight novel Meldrum's acid derivatives containing various vanillic groups were synthesized. Vanillidene Meldrum's acid compounds were tested against different cancer cell lines and microbes. Out of nine, three showed very good biological activity against E. coli, and HeLa and A549 cell lines. It is shown that the O-alkyl substituted derivatives possessed better antimicrobial and anticancer activities in comparison with the O-acyl ones. The decyl substituted molecule (3i) has the highest activity against E. coli (MIC = 12.4 µM) and cancer cell lines (HeLa, A549, and LS174 = 15.7, 21.8, and 30.5 µM, respectively). The selectivity index of 3i is 4.8 (HeLa). The molecular docking study indicates that compound 3i showed good binding affinity to DNA, E. coli Gyrase B, and topoisomerase II beta. The covalent docking showed that 3i was a Michael acceptor for the nucleophiles Lys and Ser. The best Eb was noted for the topoisomerase II beta-LYS482-3i cluster.

Efficiency of Bone Marrow-Derived Mesenchymal Stem Cells and Hesperetin in the Treatment of Streptozotocin-Induced Type 1 Diabetes in Wistar Rats.

Type 1 diabetes mellitus (T1DM) was established to be ameliorated by islet transplantation, but the shortage of the transplanted human islet tissue and the use of immunosuppressive drugs to inhibit the rejection of allogeneic grafts make this type of therapy is limited. Nowadays, therapy with stem cells is one of the most promising future treatments. This kind of therapy could have a profound impact on both replacement, as well as regenerative therapies, to improve or even cure various disorders, including diabetes mellitus. Flavonoids have also been shown to possess anti-diabetic effects. Thus, this study aims to evaluate the effectiveness of the bone marrow-derived mesenchymal stem cells (BM-MSCs) and hesperetin in the treatment of a T1DM rat model. T1DM was induced in male Wistar rats that had been starved for 16 h via intraperitoneal injection of STZ at a dose of 40 mg/kg body weight (b.wt.). After 10 days of STZ injection, the diabetic rats were allocated into four groups. The first diabetic animal group was considered a diabetic control, while the other three diabetic animal groups were treated for six weeks, respectively, with hesperetin (given orally at a dose of 20 mg/kg b.wt.), BM-MSCs (injected intravenously at a dose of 1 × 106 cells/rat/week), and their combination (hesperetin and BM-MSCs). The use of hesperetin and BM-MSCs in the treatment of STZ-induced diabetic animals significantly improved the glycemic state, serum fructosamine, insulin and C-peptide levels, liver glycogen content, glycogen phosphorylase, glucose-6-phosphatase activities, hepatic oxidative stress, and mRNA expressions of NF-κB, IL-1ß, IL-10, P53, and Bcl-2 in pancreatic tissue. The study suggested the therapy with both hesperetin and BM-MSCs produced marked antihyperglycemic effects, which may be mediated via their potencies to ameliorate pancreatic islet architecture and insulin secretory response, as well as to decrease hepatic glucose output in diabetic animals. The improvement effects of hesperetin and BM-MSCs on the pancreatic islets of diabetic rats may be mediated via their antioxidant, anti-inflammatory, and antiapoptotic actions.

Design, synthesis, and docking of novel thiazolidine-2,4-dione multitarget scaffold as new approach for cancer treatment.

Novel thiazolidine-2,4-diones have been developed and estimated as conjoint inhibitors of EGFRT790M and VEGFR-2 against HCT-116, MCF-7, A549, and HepG2 cells. Compounds 6a, 6b, and 6c were known to be the dominant advantageous congeners against HCT116 (IC50 = 15.22, 8.65, and 8.80 µM), A549 (IC50 = 7.10, 6.55, and 8.11 µM), MCF-7 (IC50 = 14.56, 6.65, and 7.09 µM) and HepG2 (IC50 = 11.90, 5.35, and 5.60 µM) mass cell lines, correspondingly. Although compounds 6a, 6b, and 6c disclosed poorer effects than sorafenib (IC50 = 4.00, 4.04, 5.58, and 5.05 µM) against the tested cell sets, congeners 6b and 6c demonstrated higher actions than erlotinib (IC50 = 7.73, 5.49, 8.20, and 13.91 µM) against HCT116, MCF-7 and HepG2 cells, yet lesser performance on A549 cells. The hugely effective derivatives 4e-i and 6a-c were inspected versus VERO normal cell strains. Compounds 6b, 6c, 6a, and 4i were found to be the most effective derivatives, which suppressed VEGFR-2 by IC50 = 0.85, 0.90, 1.50, and 1.80 µM, respectively. Moreover, compounds 6b, 6a, 6c, and 6i could interfere with the EGFRT790M performing strongest effects with IC50 = 0.30, 0.35, 0.50, and 1.00 µM, respectively. What is more, 6a, 6b, and 6c represented satisfactory in silico computed ADMET profile.

Emerging roles of tyrosine kinases in hepatic inflammatory diseases and therapeutic opportunities.

Inflammation has been convicted of causing and worsening many liver diseases like acute liver failure, fibrosis, cirrhosis, fatty liver and liver cancer. Pattern recognition receptors (PRRs) like TLRs 4 and 9 localized on resident or recruited immune cells are well known cellular detectors of pathogen and damage-associated molecular patterns (PAMPs/DAMPs). Stimulation of these receptors generates the sterile and non-sterile inflammatory responses in the liver. When these responses are repeated, there will be a sustained liver injury that may progress to fibrosis and its outcomes. Crosstalk between inflammatory/fibrogenic-dependent streams and certain tyrosine kinases (TKs) has recently evolved in the context of hepatic diseases. Because of TKs increasing importance, their role should be elucidated to highlight effective approaches to manage the diverse liver disorders. This review will give a brief overview of types and functions of some TKs like BTK, JAKs, Syk, PI3K, Src and c-Abl, as well as receptors for TAM, PDGF, EGF, VEGF and HGF. It will then move to discuss the roles of these TKs in the regulation of the proinflammatory, fibrogenic and tumorigenic responses in the liver. Lastly, the therapeutic opportunities for targeting TKs in hepatic inflammatory disorders will be addressed. Overall, this review sheds light on the diverse TKs that have substantial roles in hepatic disorders and potential therapeutics modulating their activity.

Platelet-rich Plasma in Management of Anosmia (Single Versus Double Injections).

Background: Anosmia is a common problem with a significant impact on quality of life and increased mortality. People with anosmia may not be able to fully taste foods and may lose interest in eating. This can lead to weight loss or malnutrition. Anosmia can also lead to depression because it may impair one's ability to smell or taste pleasurable foods. Platelet-rich plasma (PRP) is an autologous biologic product with anti-inflammatory and neuroprotective effects. This prospective study evaluated the role of PRP on olfactory neuroregeneration in patients with anosmia and compare the results of single and double injections. Methods: 54 patients were included in the study who had olfactory loss greater than 6 months in duration, no evidence of sinonasal inflammatory disease, and no improvement with olfactory training and topical steroids. 27 patients received a single intranasal injection of PRP into the mucosa of the olfactory cleft and 27 patients received a double injections with 3 weeks interval between them. The Q-Sticks Test was administered at the beginning of the study and at 1 and 3 months. Results: All patients reported a subjective improvement of their smell shortly after injection but then stabilized. At 3-month post-treatment, 16 patients improved significantly after single injection and 19 patients improved significantly after double injections. There were no adverse outcomes from intranasal PRP injections. Conclusion: PRP appears safe for use in the treatment of olfactory loss, and preliminary data suggest possible efficacy, especially for those with persistent loss. Further studies will help determine optimal frequency and duration of use.

Surgery Is the Last Resort for Huge Scrotal Lymphedema: A Series of Challenging Cases.

We aim to provide our surgical techniques, and outcomes of functional scrotal reduction procedures with complete preservation of the genitourinary original anatomy in a simple way without using complicated skin grafting or skin advancement flaps in Patients with huge and long-standing scrotal lymphedema 18 patients ages ranged from 14-65 with a median of 30 years. Functional scrotal and penoscrotal reduction was attained in all cases, without distortion of the genitourinary anatomy and without the need for advancement, rotational or free flaps, maximal scrotal diameter was reduced from median of 61[48-92] cms to a median of 25[21-29] cms ( P <0.0001) and remained almost unchanged at the end of the follow up period 26[22-34] cms ( P <0.0001). Sexual performance and voiding capacity were improved in all patients, testicular vascularity was unaffected and the Glasgow Benefit Inventory (GBI) for the quality of life showed marked enhancement in the total 55.5[50-72], general 55.5[50-72], social 100[50-100] and physical 16.6[16-33] points subscales. According to our experience, surgery remains the gold standard treatment for management of huge scrotal lymphedema, successful preservation of the genitourinary functions can be attained despite the size in most cases with excellent cosmoses.

Phenanthroindolizidine Alkaloids Secondary Metabolites Diversity in Medicinally Viable Plants of the Genus Tylophora.

Plants of the genus Tylophora have commonly been used in traditional medicine in various communities, especially in the tropical and subtropical regions of climatic zones. Of the nearly 300 species reported in the Tylophora genus, eight are primarily used in various forms to treat a variety of bodily disorders based on the symptoms. Certain plants from the genus have found use as anti-inflammatory, anti-tumor, anti-allergic, anti-microbial, hypoglycemic, hypolipidemic, anti-oxidant, smooth muscle relaxant, immunomodulatory, and anti-plasmodium agents, as well as free-radical scavengers. Pharmacologically, a few plant species from the genus have exhibited broad-spectrum anti-microbial and anti-cancer activity, which has been proven through experimental evaluations. Some of the plants in the genus have also helped in alcohol-induced anxiety amelioration and myocardial damage repair. The plants belonging to the genus have also shown diuretic, anti-asthmatic, and hepato-protective activities. Tylophora plants have afforded diverse structural bases for secondary metabolites, mainly belonging to phenanthroindolizidine alkaloids, which have been found to treat several diseases with promising pharmacological activity levels. This review encompasses information on various Tylophora species, their distribution, corresponding plant synonyms, and chemical diversity of the secondary metabolic phytochemicals as reported in the literature, together with their prominent biological activities.

Polymeric Nanoparticles for Delivery of Natural Bioactive Agents: Recent Advances and Challenges.

In the last few decades, several natural bioactive agents have been widely utilized in the treatment and prevention of many diseases owing to their unique and versatile therapeutic effects, including antioxidant, anti-inflammatory, anticancer, and neuroprotective action. However, their poor aqueous solubility, poor bioavailability, low GIT stability, extensive metabolism as well as short duration of action are the most shortfalls hampering their biomedical/pharmaceutical applications. Different drug delivery platforms have developed in this regard, and a captivating tool of this has been the fabrication of nanocarriers. In particular, polymeric nanoparticles were reported to offer proficient delivery of various natural bioactive agents with good entrapment potential and stability, an efficiently controlled release, improved bioavailability, and fascinating therapeutic efficacy. In addition, surface decoration and polymer functionalization have opened the door to improving the characteristics of polymeric nanoparticles and alleviating the reported toxicity. Herein, a review of the state of knowledge on polymeric nanoparticles loaded with natural bioactive agents is presented. The review focuses on frequently used polymeric materials and their corresponding methods of fabrication, the needs of such systems for natural bioactive agents, polymeric nanoparticles loaded with natural bioactive agents in the literature, and the potential role of polymer functionalization, hybrid systems, and stimuli-responsive systems in overcoming most of the system drawbacks. This exploration may offer a thorough idea of viewing the polymeric nanoparticles as a potential candidate for the delivery of natural bioactive agents as well as the challenges and the combating tools used to overcome any hurdles.

Royal Jelly and Chlorella vulgaris Mitigate Gibberellic Acid-Induced Cytogenotoxicity and Hepatotoxicity in Rats via Modulation of the PPARα/AP-1 Signaling Pathway and Suppression of Oxidative Stress and Inflammation.

Gibberellic acid (GA3) is a well-known plant growth regulator used in several countries, but its widespread use has negative effects on both animal and human health. The current study assesses the protective effect of royal jelly (RJ) and Chlorella vulgaris (CV) on the genotoxicity and hepatic injury induced by GA3 in rats. Daily oral administration of 55 mg/kg GA3 to rats for 6 constitutive weeks induced biochemical and histopathological changes in the liver via oxidative stress and inflammation. Co-administration of 300 mg/kg RJ or 500 mg/kg CV with GA3 considerably ameliorated the serum levels of AST (aspartate aminotransferase), ALT (alanine aminotransferase), ALP (alkaline phosphatase), γGT (gamma-glutamyl transferase), total bilirubin, and albumin. Lowered malondialdehyde, tumor necrosis factor α (TNF-α), and nuclear factor κB (NF-κB) levels along with elevated SOD (superoxide dismutase), CAT (catalase), and GPx (glutathione peroxidase) enzyme activities indicated the antioxidant and anti-inflammatory properties of both RJ and CV. Also, they improved the histological structure and reduced cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expressions along with up-regulating peroxisome proliferator activated receptor α (PPARα) and down-regulating activator protein 1 (AP-1) gene expression. Additionally, chromosomal abnormalities and mitotic index were nearly normalized after treatment with RJ and CV. In conclusion, RJ and CV can protect against GA3-induced genotoxicity and liver toxicity by diminishing oxidative stress and inflammation, and modulating the PPARα/AP-1 signaling pathway.

Exploring the potential of quercetin/aspirin-loaded chitosan nanoparticles coated with Eudragit L100 in the treatment of induced-colorectal cancer in rats.

Growing evidence suggests quercetin and aspirin may have anticancer properties, notably in the case of colorectal cancer. The goal of this study was to create Pluronic F127 and polyethylene glycol4000 solid dispersion-loaded chitosan nanoparticles for colonic quercetin and aspirin delivery. In 1:1 polymeric stoichiometric ratio, solubility and complex formation were verified. Solid dispersion-loaded chitosan nanoparticles with a diameter of 244.45 ± 8.5 nm, a surface charge of 34.1 ± 3.3 mV, and encapsulation effectiveness of 76.3 ± 4.3% were generated under ideal conditions. In some cases, coating with Eudragit L100 resulted in a decrease in zeta potential and an increase in particle size. The coated formulation released the actives in a pH-dependent manner, considering their physicochemical features. Surprisingly, when compared to the actives' suspension and uncoated formulation, the coated formulation had greater anti-inflammatory efficacy, with a substantial reduction of PGE2 and IL-8 production in colonic tissues (16.9 ± 7.9 ng/g tissue and 134.9 ± 10.1 pg/g tissue, respectively). It also reversed most of the dimethyl hydrazine-induced histological alterations in the colon. It also demonstrated a greater reduction in TNF expression in colonic tissues. As a result, Eudragit L100-coated QT/AS-loaded chitosan nanoparticles are suggested to provide a potential platform for colonic delivery of quercetin and aspirin.