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Receptor tyrosine kinases (RTKs) are transmembrane cell-surface proteins that act as signal transducers. They regulate essential cellular processes like proliferation, apoptosis, differentiation and metabolism. RTK alteration occurs in a broad spectrum of cancers, emphasising its crucial role in cancer progression and as a suitable therapeutic target. The use of small molecule RTK inhibitors however, has been crippled by the emergence of resistance, highlighting the need for a pleiotropic anti-cancer agent that can replace or be used in combination with existing pharmacological agents to enhance treatment efficacy. Curcumin is an attractive therapeutic agent mainly due to its potent anti-cancer effects, extensive range of targets and minimal toxicity. Out of the numerous documented targets of curcumin, RTKs appear to be one of the main nodes of curcumin-mediated inhibition. Many studies have found that curcumin influences RTK activation and their downstream signaling pathways resulting in increased apoptosis, decreased proliferation and decreased migration in cancer both in vitro and in vivo. This review focused on how curcumin exhibits anti-cancer effects through inhibition of RTKs and downstream signaling pathways like the MAPK, PI3K/Akt, JAK/STAT, and NF-κB pathways. Combination studies of curcumin and RTK inhibitors were also analysed with emphasis on their common molecular targets.

Sphaeranthus indicus L. is a medicinal herb having widespread traditional uses for treating common ailments. The present research work aims to explore the in-depth phytochemical composition and in vitro reactivity of six different polarity solvents (methanol, n-hexane, benzene, chloroform, ethyl acetate, and n-butanol) extracts/fractions of S. indicus flowers. The phytochemical composition was accomplished by determining total bioactive contents, HPLC-PDA polyphenolic quantification, and UHPLC-MS secondary metabolomics. The reactivity of the phenolic compounds was tested through the following biochemical assays: antioxidant (DPPH, ABTS, FRAP, CUPRAC, phosphomolybdenum, and metal chelation) and enzyme inhibition (AChE, BChE, α-glucosidase, α-amylase, urease, and tyrosinase) assays were performed. The methanol extract showed the highest values for phenolic (94.07 mg GAE/g extract) and flavonoid (78.7 mg QE/g extract) contents and was also the most active for α-glucosidase inhibition as well as radical scavenging and reducing power potential. HPLC-PDA analysis quantified rutin, naringenin, chlorogenic acid, 3-hydroxybenzoic acid, gallic acid, and epicatechin in a significant amount. UHPLC-MS analysis of methanol and ethyl acetate extracts revealed the presence of well-known phytocompounds; most of these were phenolic, flavonoid, and glycoside derivatives. The ethyl acetate fraction exhibited the highest inhibition against tyrosinase and urease, while the n-hexane fraction was most active for α-amylase. Moreover, principal component analysis highlighted the positive correlation between bioactive compounds and the tested extracts. Overall, S. indicus flower extracts were found to contain important phytochemicals, hence could be further explored to discover novel bioactive compounds that could be a valid starting point for future pharmaceutical and nutraceuticals applications.

This study sets out to probe into total bioactive contents, UHPLC-MS secondary metabolites profiling, antioxidant (DPPH, ABTS, FRAP, CUPRAC, phosphomolybdenum and metal chelating) and enzyme inhibi...

In this study, different parts (aerial, stem and root) of Salvadora oleoides Decne were investigated in order to explore their phytochemical composition and biological potential. The bioactive contents were evaluated by conventional spectrophotometric methods. Additionally, the secondary metabolite compounds were identified by UHPLC-MS analysis. Biological potential was evaluated by determining antioxidant (DPPH, FRAP, and Phosphomolybdenum) and enzyme inhibitory (butrylcholinesterase and lipoxygenase) effects. Higher total bioactive contents were found in methanolic extracts which tend to correlate with higher radical scavenging and reducing potential of these extracts. LC/MS spectrum revealed the presence of 16 different secondary metabolites belonging to terpene, glucoside and sesquiterpenoid dervivatives. Glucocleomin and emotin A were the main compounds present in all three parts. The strongest butrylcholinesterase and lipoxygenase inhibitory activity was observed for root and stem DCM extracts. Demonstrated biological potential of S. oleoides plant can trace a new road map for developing newly designed bioactive pharmaceuticals.

Mechanical wounding is the major trigger for the formation of agarwood in the tropical tree taxon Aquilaria. To understand the molecular mechanism by which Aquilaria reacts to wounding, we applied a proteomics approach using liquid chromatography electrospray-ionization coupled with tandem mass spectrometry (LC-MS/MS) coupled with bioinformatics analysis and principal component analysis. Protein samples were extracted from wood tissues collected from drilled wounds on the stems of five-year old Aquilaria malaccensis. Samples were collected at different time-points of 0, 2, 6, 12, and 24 h after mechanical wounding for protein identification. Venn diagram analysis showed that 564 out of 2227 identified proteins were time-point specific proteins. GO analysis using the REViGO software (including functional proteins) supported these findings. In total, 20 wound-response proteins and one unknown protein were identified as having important roles in the signaling response to wounding, response to stress, activation of plant defense systems, and plant regeneration. The detected biological processes include brassinosteroid stimulus, polyamine catabolism, hypersensitive response, response to cadmium ions, response to oxidative stress, and malate metabolism, suggesting that the wounded trees must have undergone major plant cell damage. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that several wound-response proteins were involved in agarwood formation. Our proteomics data thus provide useful information for understanding the wound response mechanisms that trigger agarwood formation.

Background Ethnobotanical and plant-based products allow for the isolation of active constituents against a number of maladies. Monotheca buxifolia is used by local communities due to its digestive and laxative properties, as well as its ability to cure liver, kidney, and urinary diseases. There is a need to explore the biological activities and chemical constituents of this medicinal plant. Methods In this work, the biochemical potential of M. buxifolia (Falc.) A. DC was explored and linked with its biological activities. Methanol and chloroform extracts from leaves and stems were investigated for total phenolic and flavonoid contents. Ultrahigh-performance liquid chromatography coupled with mass spectrometry (UHPLC–MS) was used to determine secondary-metabolite composition, while high-performance liquid chromatography coupled with photodiode array detection (HPLC–PDA) was used for polyphenolic quantification. In addition, we carried out in vitro assays to determine antioxidant potential and the enzyme-inhibitory response of M. buxifolia extracts. Results Phenolics (91 mg gallic-acid equivalent (GAE)/g) and flavonoids (48.86 mg quercetin equivalent (QE)/g) exhibited their highest concentration in the methanol extract of stems and the chloroform extract of leaves, respectively. UHPLC–MS analysis identified a number of important phytochemicals, belonging to the flavonoid, phenolic, alkaloid, and terpenoid classes of secondary metabolites. The methanol extract of leaves contained a diosgenin derivative and polygalacin D, while kaempferol and robinin were most abundant in the chloroform extract. The methanol extract of stems contained a greater peak area for diosgenin and kaempferol, whereas this was true for lucidumol A and 3-O-cis-coumaroyl maslinic acid in the chloroform extract. Rutin, epicatechin, and catechin were the main phenolics identified by HPLC–PDA analysis. The methanol extract of stems exhibited significant 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical-scavenging activities (145.18 and 279.04 mmol Trolox equivalent (TE)/g, respectively). The maximum cupric reducing antioxidant capacity (CUPRAC) (361.4 mg TE/g), ferric-reducing antioxidant power (FRAP) (247.19 mg TE/g), and total antioxidant potential (2.75 mmol TE/g) were depicted by the methanol extract of stems. The methanol extract of leaves exhibited stronger inhibition against acetylcholinesterase (AChE) and glucosidase, while the chloroform extract of stems was most active against butyrylcholinesterase (BChE) (4.27 mg galantamine equivalent (GALAE)/g). Similarly, the highest tyrosinase (140 mg kojic-acid equivalent (KAE)/g) and amylase (0.67 mmol acarbose equivalent (ACAE)/g) inhibition was observed for the methanol extract of stems. Conclusions UHPLC–MS analysis and HPLC–PDA quantification identified a number of bioactive secondary metabolites of M. buxifolia, which may be responsible for its antioxidant potential and enzyme-inhibitory response. M. buxifolia can be further explored for the isolation of its active components to be used as a drug.

Breast cancer is the abnormal, uncontrollable proliferation of cells in the breast. Conventional treatment modalities like chemotherapy induce deteriorating side effects on healthy cells. Non-viral inorganic nanoparticles (NPs) confer exclusive characteristics, such as, stability, controllable shape and size, facile surface modification, and unique magnetic and optical properties which make them attractive drug carriers. Among them, carbonate apatite (CA) particles are pH-responsive in nature, enabling rapid intracellular drug release, but are typically heterogeneous with the tendency to self-aggregate. Here, we modified the nano-carrier by partially substituting Ca2+ with Mg2+ and Fe3+ into a basic lattice structure of CA, forming Fe/Mg-carbonate apatite (Fe/Mg-CA) NPs with the ability to mitigate self-aggregation, form unique protein corona in the presence of serum and efficiently deliver doxorubicin (DOX), an anti-cancer drug into breast cancer cells. Two formulations of Fe/Mg-CA NPs were generated by adding different concentrations of Fe3+ and Mg2+ along with a fixed amount of Ca2+ in bicarbonate buffered DMEM (Dulbecco&rsquo, s Modified Eagle&rsquo, s Medium), followed by 30 min incubation at 37 &deg, C. Particles were characterized by turbidity analysis, z-average diameter and zeta potential measurement, optical microscopy, field emission scanning electron microscopy (FESEM), Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray (EDX), flame atomic absorption spectroscopy (FAAS), pH dissolution, drug binding, cellular uptake, thiazolyl blue tetrazolium bromide (MTT) assay, stability analysis, and protein corona study by LCMS (Liquid chromatography-mass spectrometry). Both formulations of Fe/Mg-CA displayed mostly uniform nano-sized particles with less tendency to aggregate. The EDX and FAAS elemental analysis confirmed the weight (%) of Ca, Fe and Mg, along with their Ca/P ratio in the particles. A constant drug binding efficiency was noticed with 5 &mu, M to 10 &mu, M of initial DOX concentration. A pH dissolution study of Fe/Mg-CA NPs revealed the quick release of DOX in acidic pH. Enhancement of cytotoxicity for the chemotherapy drug was greater for Fe/Mg-CA NPs as compared to CA NPs, which could be explained by an increase in cellular internalization as a result of the small z-average diameter of the former. The protein corona study by LCMS demonstrated that Fe/Mg-CA NPs exhibited the highest affinity towards transport proteins without binding with opsonins. Biodistribution study was performed to study the effect of DOX-loaded Fe/Mg-CA NPs on the tissue distribution of DOX in Balb/c 4T1 tumor-bearing mice. Both formulations of Fe/Mg-CA NPs have significantly increased the accumulation of DOX in tumors. Interestingly, high Fe/Mg-CA NPs exhibited less off-target distribution compared to low Fe/Mg-CA NPs. Furthermore, the blood plasma analysis revealed prolonged blood circulation half-life of DOX-loaded low and high Fe/Mg-CA NPs compared to free DOX solution. Modifying CA NPs with Fe3+ and Mg2+, thereby, led to the generation of nano-sized particles with less tendency to aggregate, enhancing the drug binding efficiency, cellular uptake, and cytotoxicity without hampering drug release in acidic pH, while improving the circulation half-life and tumor accumulation of DOX. Therefore, Fe/Mg-CA which predominantly forms a transport protein-related protein corona could be a proficient carrier for therapeutic delivery in breast cancer.

Capparis spinose L. also known as Caper is of great significance as a traditional medicinal food plant. The present work was targeted on the determination of chemical composition, pharmacological properties, and in-vitro toxicity of methanol and dichloromethane (DCM) extracts of different parts of C. spinosa. Chemical composition was established by determining total bioactive contents and via UHPLC-MS secondary metabolites profiling. For determination of biological activities, antioxidant capacity was determined through DPPH, ABTS, CUPRAC, FRAP, phosphomolybdenum, and metal chelating assays while enzyme inhibition against cholinesterase, tyrosinase, α-amylase and α-glucosidase were also tested. All the extracts were also tested for toxicity against two breast cell lines. The methanolic extracts were found to contain highest total phenolic and flavonoids which is correlated with their significant radical scavenging, cholinesterase, tyrosinase and glucosidase inhibition potential. Whereas DCM extracts showed significant activity for reducing power, phosphomolybdenum, metal chelation, tyrosinase, and α-amylase inhibition activities. The secondary metabolites profiling of both methanolic extracts exposed the presence of 21 different secondary metabolites belonging to glucosinolate, alkaloid, flavonoid, phenol, triterpene, and alkaloid derivatives. The present results tend to validate folklore uses of C. spinose and indicate this plant to be used as a potent source of designing novel bioactive compounds.

1st International Conference on Natural Toxicology and Pharmacology (ICNTP) -- AUG 08-12, 2019 -- Guangzhou, PEOPLES R CHINA, WOS: 000482246600053, PubMed: 31154083, This study endeavours to investigate the phytochemical composition, biological properties and in vivo toxicity of methanol and dichloromethane extracts of Zaleya pentandra (L.) Jeffrey. Total bioactive contents, antioxidant (phosphomolybdenum and metal chelating, DPPH, ARTS, FRAP and CUPRAC) and enzyme inhibition (cholinesterases, tyrosinase alpha-amylase, and alpha-glucosidase) potential were assessed utilizing in vitro bioassays. UHPLC-MS phytochemical profiling was carried out to identify the essential compounds. The methanol extract was found to contain highest phenolic (22.60 mg GAE/g) and flavonoid (31.49 mg QE/g) contents which correlate with its most significant radical scavenging, reducing potential and tyrosinase inhibition. The dichloromethane extract was most potent for phosphomolybdenum, ferrous chelation, alpha-amylase, alpha-glucosidase, and cholinesterase inhibition assays. UHPLC-MS analysis of methanol extract unveiled to identify 11 secondary metabolites belonging to five sub-groups, i.e., phenolic, alkaloid, carbohydrate, terpenoid, and fatty acid derivatives. Additionally, in vivo toxicity was conducted for 21 days and the methanol extract at different doses (150, 200, 250 and 300 mg/kg) was administered in experimental chicks divided into five groups each containing five individuals. Different physical, haematological and biochemical parameters along with the absolute and relative weight of visceral body organs were studied. Overall, no toxic effect was noted for the extract at tested doses., Jinan Univ, Zhejiang Univ, Univ Macau, Univ Hong Kong, Int Assoc Dietet Nutr & Safety, Int Soc Chinese Med

WOS: 000499762200024, The plants of genus Neurada have been utilized for medicinal purposes. This study probed into the biological propensities and endeavored to achieve the detailed phytochemical profile, via ultra-high performance liquid chromatography -UHPLC-MS analysis and high performance liquid chromatography photodiode array -HPLC-PDA of different polarity extracts (methanol, n-hexane, chloroform, and n-butanol) of Nevada procumbens L. The biological features were studied by determining the antioxidant potential via 2,2-Diphenyl-1-picrylhydrazyl-DPPH, 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid -ABTS, ferric reducing antioxidant power -FRAP, cupric reducing antioxidant power -CUPRAC, phoshomolybdenum and metal chelation assays and clinically significant major enzymes (cholinesterases, alpha-amylase, alpha-glucosidase and tyrosinase inhibition). Moreover, the correlation among the biological activities and total bioactive contents of the extracts were studied via multivariate statistical analysis. The methanol and n-butanol extracts revealed the presence of total phenolic and flavonoid contents in highest concentrations which tend to correlate with their maximum anti-oxidant capacities for radical scavenging and reducing power assays. The n-hexane extract was most active in the phosphomolybdenum assays whereas the chloroform extracts showed the highest metal chelation potential. The UHPLC-MS phytochemical profiling of the methanolic extract (both positive and negative ionization mode) revealed the existence of eighteen phytochemicals representing four different classes (phenolics, flavonoids, sesquiterpenoids, and alkaloids). The n-butanol extract inhibited acetylcholinesterase (4.10 mg galantamine equivalent -GALAE/g) and tyrosinase (127.65 mg kojic acid equivalent -KAE/g) significantly as compared to the control. The n-hexane extract exhibited highest inhibition against butyrylcholinesterase (1.93 mg GALAE/g) and alpha-glucosidase (59.0 mmol acarbose equivalent -ACAE/g), while chloroform extract exhibited prominent inhibitory action inimical to alpha-amylase (0.65 mmol ACAE/g). Overall, it was observed that FRAP and tyrosinase activities were the most contributive biological activities for the formation of first component with p values of 0.018 and 0.023, respectively, whereas, for the formation of second component, glucosidase activity was the most contributive assay with p value of 0.002. It can be concluded that the manifestation of dynamic phytochemicals with multi-pharmacological potential marks N. procumbens as a prospective origin of health-promoting molecules warrants further exploration as a unique therapeutic medicinal plant.

WOS: 000458942600002, The plants of Euphorbia genus have been extensively studied for their nutritive and therapeutic purposes. The present research is the foremost effort to investigate and compare the biological activities and chemical composition of dichloromethane (DCM) and methanol (MeOH) solvent extracts of Euphorbia milii Des Moul aerial and root parts. Antioxidant potential was determined using six different (FRAP, CUPRAC, Phosphomolybdenum, DPPH, ABTS and ferrous chelation) methods. The enzyme inhibition effects of the tested extracts were evaluated against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), alpha-glucosidase, alpha-amylase and tyrosinase. Similarly, the amount of total phenolic and flavonoid contents were assessed via spectrophotometric methods and individual secondary metabolites were also determined using UHPLC-MS analysis. Methanolic extracts from both aerial and root parts contained the highest contents for phenolic and flavonoids which tends to correlate with their significant DPPH, ABTS (radical scavenging), FRAP, CUPRAC (reducing power) and alpha-glucosidase inhibition potentials. While, both the DCM extracts containing the lowest bioactive contents were most active in the phosphomolybdenum assay, cholinesterases and tyrosinase inhibition. The root extracts proved to be a better source of bioactive antioxidant molecules. Additionally, UHPLC-MS profiling of both the methanolic extracts revealed the presence of total 16 secondary metabolites belonging to five major groups (phenolic, flavonoid, coumarin, glycoside and alkaloid). To conclude, our results suggest that E. milii can be considered as a promising lead origin for natural bioactive enzyme inhibitory and antioxidant compounds which could pave the way for industrial applications.

Calligonum polygonoides L. also known as famine food plant, is normally consumed in times of food scarcity in India and Pakistan and also used traditionally in the management of common diseases. The present design aims to provide an insight into the medicinal potential of four solvent extracts of C. polygonoides via an assessment of its phytochemical profile, antioxidant and enzyme inhibitory potential. Phytochemical composition was estimated by deducing total bioactive constituents, UHPLC-MS secondary metabolites profile, and HPLC phenolic quantification. Antioxidant potential was determined via six methods (radical scavenging (DPPH and ABTS), reducing power (FRAP and CUPRAC), phosphomolybdenum total antioxidant capacity and metal chelation activity). Enzyme inhibitory potential was assessed against clinical enzymes (acetylcholinesterase -AChE, butyrylcholinesterase -BChE, tyrosinase, and α-amylase). The highest amounts of phenolic contents were found in chloroform extract (76.59 mg GAE/g extract) which may be attributed to its higher radical scavenging, reducing power and tyrosinase inhibition potential. The n-butanol extract containing the maximum amount of flavonoids (55.84 mg RE/g extract) exhibited highest metal chelating capacity. Similarly, the n-hexane extract was found to be most active against AChE (4.65 mg GALAE/g extract), BChE (6.59 mg GALAE/g extract), and α-amylase (0.70 mmol ACAE/g extract) enzymes. Secondary metabolite assessment of the crude methanol extract as determined by UHPLC-MS analysis revealed the presence of 24 (negative ionization mode) and 15 (positive ionization mode) secondary metabolites, with most of them belonging to phenolic, flavonoids, terpene, and alkaloid groups. Moreover, gallic acid and naringenin were the main phenolics quantified by HPLC-PDA analysis in all the tested extracts (except n-butanol extract). PCA statistical analysis was also conducted to establish any possible relationship amongst bioactive contents and biological activities. Overall, the C. polygonoides extracts could be further considered to isolate bioactive enzyme inhibitory and antioxidant natural phytocompounds.

The current research work is an endeavor to study the chemical profiling and enzyme-inhibition potential of different polarity solvent (n-hexane, dichloromethane—DCM and methanol—MeOH) extracts from the aerial and stem parts of Buxus papillosa C.K. Schneid. All the extracts were analyzed for HPLC-PDA phenolic quantification, while both (aerial and stem) DCM extracts were studied for UHPLC-MS phytochemical composition. The inhibitory activity against the clinically important enzymes having crucial role in different pathologies like skin diseases (tyrosinase), inflammatory problems (lipoxygenase—LOX) and diabetes mellitus (α-amylase) were studied using standard in vitro bioassays. The DCM extracts upon UHPLC-MS analysis conducted in both negative and positive ionization modes has led to the tentative identification of 52 important secondary metabolites. Most of these belonged to the alkaloid, flavonoid, phenolic and triterpenoid classes. The HPLC-PDA polyphenolic quantification identified the presence of 10 phenolic compounds. Catechin was present in significant amounts in aerial-MeOH (7.62 ± 0.45 μg/g extract) and aerial-DCM (2.39 ± 0.51-μg/g extract) extracts. Similarly, higher amounts of epicatechin (2.76 ± 0.32-μg/g extract) and p-hydroxybenzoic acid (1.06 ± 0.21 μg/g extract) were quantified in aerial-DCM and stem-MeOH extracts, respectively. Likewise, all the extracts exhibited moderate inhibition against all the tested enzymes. These findings explain the wide usage of this plant in folklore medicine and suggest that it could be further studied as an origin of novel bioactive phytocompounds and for the designing of new pharmaceuticals.