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Purpose: To investigate the wound-healing potential of herbal formulations (emulgels and in situ gels) containing Saussurea lappa root extract (SLRE) via excision wound induction in albino rats. Methods: Preliminary phytochemical analysis of the methanol extract of roots of Saussurea lappa (SLRE) was performed using standard procedures. In vitro anti-inflammatory assay of SLRE was conducted using heat-induced hemolysis method at a concentration of 100 μg/mL. Acute toxicity of SLRE was also evaluated in mice at a single dose of 1000 mg/kg for 24 h. Emulgels and in situ gels were prepared using different concentrations of SLRE and assessed for their organoleptic and physical properties. In vitro drug release studies of the prepared formulations were carried out by Franz diffusion cell and the data fitted into various pharmacokinetic models. Wound healing was assessed using excision wound induction (380 mm2) on dorsal surface of male albino rats. Each formulation (F4, F5, F6, G1, G2 and G3) and pyodine gel (standard) were applied topically (0.5 g) for 20 days. Wound contraction was measured every fourth day. Results: SLRE showed 42.8 % inhibition in heat-induced hemolysis on erythrocyte membrane model, compared to aspirin (positive control). Moreover, SLRE did not cause mortality in mice at the given doses. All the formulations were stable after one month stability check at 40 °C for emulgels and at 25 °C for in situ gels. All the formulations followed first order drug release pattern. In situ gel (G3) exhibited better wound healing (100 ± 0.0028) than emulgel (F6, 99 ± 0.004) containing 5 g extract and standard pyodine gel (91 ± 0.014, p

In search of suitable therapy for the management of Alzheimer’s disease, this study was designed to evaluate metal complexes against its biochemical targets. Zinc metal carboxylates (AAZ1–AAZ6) wer...

With the recent technological advancements, a new golden era of natural products drug discovery has dawned. Increasingly it is being realized that structural modularity of many pharmacologically active products derived natural sources allows a building-block approach which can be exploited for analysis of regulation of deregulated oncogenic protein networks in different cancers. Piceatannol has been shown to effectively modulate JAK/STAT, Wnt/β-catenin, mTOR pathway in different cancers. In addition, certain hints have emerged which shed light on the regulation of microRNAs by piceatannol in some cancers. Regulation of deregulated oncogenic pathways by Piceatannol is gradually capturing attention and might be helpful in the multi-targeting of deregulated oncogenic networks in cancers.

It is becoming progressively more understandable that pharmaceutical targeting of drug-resistant cancers is challenging because of intra- and inter-tumor heterogeneity. Interestingly, naturally derived bioactive compounds have unique ability to modulate wide-ranging deregulated oncogenic cell signaling pathways. In this review, we have focused on the available evidence related to regulation of PI3K/AKT/mTOR, Wnt/β-catenin, NF-κB and TRAIL/TRAIL-R by fisetin in different cancers. Fisetin has also been shown to inhibit the metastatic spread of cancer cells in tumor-bearing mice. We have also summarized how fisetin regulated autophagy in different cancers. In addition, this review also covers fisetin-mediated regulation of VEGF/VEGFR, EGFR, necroptosis and Hippo pathway. Fisetin has entered into clinical trials particularly in context of COVID19-associated inflammations. Furthermore, fisetin mediated effects are also being tested in clinical trials with reference to osteoarthritis and senescence. These developments will surely pave the way for full-fledge and well-designed clinical trials of fisetin in different cancers. However, we still have to comprehensively analyze and fully unlock pharmacological potential of fisetin against different oncogenic signaling cascades and non-coding RNAs. Fisetin has remarkable potential as chemopreventive agent and future studies must converge on the identification of additional regulatory roles of fisetin for inhibition and prevention of cancers.

Three new bioactive metabolites, 1,6-dihydroxy- 2-methyl-heptan-4-one (1), 4-hydroxy-1-(2-methyl-oxiranyl)- pentan-2-one (2), and 2-(2-hydroxy-propyl)-4-methylfuran- 3-carboxylic acid amide (3) were isolated from the terrestrial Streptomyces sp. isolate ANK245, along with the new microbial constituent p-vinylanisol (4a) and the known metabolites p-vinyl-phenol (4b) and phenethyl alcohol. Analysis of the nonpolar part of the extract by gas chromatography/mass spectrometry (GC-MS) provided further evidence for tetradecanoic acid, 9-octadecenoic acid, hexadecanoic acid, 2-methoxy-4-vinylphenol (4c), 4-hydroxy-3-methoxy-benzaldehyde, o-hydroxybiphenyl, and 1,5,9-trimethyl-4,8,13-cyclotetradecatrien-1,3-diol (5). Structures 1–3 of the new compounds were elucidated by nuclear magnetic resonance (NMR) and NMR spectroscopy, but mass spectrometry (MS) techniques and their absolute configuration were determined by density functional theory (DFT) calculations and Mosher derivatisation. Their antimicrobial and cytotoxic activities were evaluated in comparison with the crude bacterial extract.

There has always been a keen interest of basic and clinical researchers to search for cancer therapeutics having minimum off-target effects and maximum anticancer activities. In accordance with this approach, there has been an explosion in the field of natural products research in the past few decades because of extra-ordinary list of natural extracts and their biologically and pharmacologically active constituents having significant medicinal properties. Apparently, luteolin-mediated anticancer effects have been investigated in different cancers but there is superfluousness of superficial data. Generalized scientific evidence encompassing apoptosis, DNA damage and anti-inflammatory effects has been reported extensively. However, how luteolin modulates deregulated oncogenic pathways in different cancers has not been comprehensively uncovered. In this review we have attempted to focus on cutting-edge research which has unveiled remarkable abilities of luteolin to modulate deregulated oncogenic pathways in different cancers. We have partitioned the review into various sections to separately discuss advancements in therapeutic targeting of oncogenic protein networks. We have provided detailed mechanistic insights related to JAK-STAT signaling and summarized how luteolin inhibited STAT proteins to inhibit STAT-driven gene network. We have also individually analyzed Wnt/β-catenin and NOTCH pathway and how luteolin effectively targeted these pathways. Mapping of the signaling landscape has revealed that NOTCH pathway can be targeted therapeutically. NOTCH pathway was noted to be targeted by luteolin. We have also conceptually analyzed how luteolin restored TRAIL-induced apoptosis in resistant cancers. Luteolin induced an increase in pro-apoptotic proteins and efficiently inhibited anti-apoptotic proteins to induce apoptosis. Luteolin mediated regulation of non-coding RNAs is an exciting and emerging facet. Excitingly, there is sequential and systematic accumulation of clues which have started to shed light on intricate regulation of microRNAs by luteolin in different cancers. Collectively, sophisticated information will enable us to develop a refined understanding of the multi-layered regulation of signaling pathways and non-coding RNAs by luteolin in different cancers.

Purpose : To investigate the antihyperglycemic activity of Conyza canadensis via α-glucosidase inhibition in alloxan-induced diabetic mice. Methods : In vitro antidiabetic activity was investigated using α-glucosidase inhibition assay with acarbose (62.5, 125, 500 and 1000 μg/ml) as the standard drug. Conyza canadensis crude extract (Cc.Cr) in doses of 10, 30, 100 and 300 mg/kg were administered daily as a single dose to alloxaninduced (200 mg/kg) diabetic mice (Balb/c), and its effect on fasting blood glucose levels and body weight were evaluated for 15 consecutive days; oral glucose tolerance test was conducted. Metformin (500 mg/kg) was used as a standard antidiabetic drug for comparison. Acute toxicity of Cc.Cr was also evaluated at doses of 3 and 5 g/kg. Results : Conyza canadensis crude extract (Cc.Cr) exhibited strong enzyme inhibition at concentrations (μg/ml) of 1000 (74.78 ± 0.92), 500 (65.11 ± 0.07), 250 (57.55 ± 0.41), 125 (51.55 ± 0.67) and 62.5 ( 44.00 ± 0.57), with a median inhibitory concentration (IC 50 ) of 107 μg/ml. Cc.Cr at all test doses (10 - 300 mg / kg) reduced fasting blood glucose levels in alloxan (200 mg/kg) - induced diabetic mice on days 5, 10 and 15 compared to the diabetic control group (p < 0. 001). These effects were similar to those caused by the standard antidiabetic drug, metformin. Cc.Cr at all test doses also increased body weight of treated animals. The extract (300 mg/kg) significantly improved tolerance of oral glucose overload in mice, like metformin. The extract did not cause any mortality up to the maximum dose of 5 g/kg. Conclusion : The results reveal that Conyza canadensis possesses potent secondary metabolites which can cause inhibition of α-glucosidase. Moreover, the plant extract has the ability to reduce blood glucose level in diabetic animals and significantly improves oral glucose overload tolerance. Keywords : Conyza canadensis , α-Glucosidase, Blood glucose, Alloxan, Diabetes, Glucose tolerance

Purpose: To investigate the possible hepatoprotective potential of Parthenium hysterophorus crude extract (Ph.Cr) against carbon tetrachloride (CCL4)- and paracetamol-induced hepatotoxicity in rabbits.Methods: Twenty rabbits were divided into five groups of four rabbits each. Group 1 served as normal control and received normal saline (5 mL/kg). Group 2 received normal saline followed by CCL4 (0.75 mL/kg p.o dose) after 1 h. Groups 3 and 4 received Ph.Cr at doses of 15 and 30 mg/kg po, respectively, for 7 days followed by one dose of CCL4, 2 h after the last extract dose (0.75 mL/kg, sc). Group 5 received silymarin as reference standard at a dose of 100 mg/kg orally for 7 days followed by one dose of CCL4 (0.75 mL/kg, sc), 2 h after the last drug dose. The effect of the extract on potassium (K+)- induced contractions in isolated rabbit jejenum was also evaluated. At the end of the study, the animals were sacrificed and their liver architecture examined microscopically.Results: Pre-treatment of rabbits with Ph.Cr reduced ALT, ALP and TB levels (p < 0.05, p < 0.01, p < 0.001) dose dependently. Hepatoprotective data indicate that Ph.Cr markedly reduced CCL4- and paracetamol-induced toxicity by preserving the histological architecture of the liver tissue at near normal. In isolated rabbit jejunum tissue, Ph.Cr relaxed high K+ (80 Mm)-induced contractions in a concentration-dependent (0.03 - 10 mg/mL) manner like that caused by silymarin.Conclusion: In the light of the results obtained, Parthenium hysterophorous possesses hepatoprotective activity against CCL4- and paracetamol-induced hepatic damage, possibly mediated via its antioxidant and Ca++ antagonist mechanisms.Keywords: Parthenium hysterophorus, Toxins, Hepatoprotection, Ca++ antagonist, Silymarin