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Background/Objectives: Inflammation and analgesia are two prominent symptoms and often lead to chronic medical conditions. To control inflammation and analgesia, many marketed drugs are in practice but the majority of them have severe side effects. Methods: This study involved the synthesis of a pivalate-based Michael product and evaluated it for in vitro COX-1, COX-2, and 5-LOX inhibitory potentials using specific assays. Molecular docking studies were also assessed. Based on the in vitro results, the compound was also subjected to in vivo anti-inflammatory and antinociceptive studies. Results: The pivalate-based Michael product (MAK01) was synthesized by an organocatalytic asymmetric Michael addition of ethyl isobutyrate to N-phenylmaleimide with an isolated yield of 96%. The structure of the compound was confirmed through 1H and 13C NMR analyses. The observed IC50 values for COX-1, COX-2, and 5-LOX were 314, 130, and 105 μg/mL, respectively. The molecular docking studies on the synthesized compound showed binding interactions with the minimized pockets of the respective enzymes. In a carrageenan model, a percent reduction in edema when administered at 10 mg/kg (a reduction of 33.3 ± 0.77% at the second hour), 20 mg/kg (a reduction of 34.7 ± 0.74% at the second hour), and 30 mg/kg (a reduction of 40.58% ± 0.84% after the fifth hour) was observed. The compound showed a significant response at concentrations of 50, 100, and 150 mg/kg with latency times of 10.32 ± 0.82, 12.16 ± 0.51, and 12.93 ± 0.45 s, respectively. Conclusion: In this study, we synthesized a pivalate-based Michael product for the first time. Moreover, based on its rationality and potency, it was found to be an effective future medicine for the management of analgesia and inflammation.

Purpose of current study was to determine physicochemical, triglyceride composition, and functional groups of wild adlay accessions (brown, black, yellow, grey, green, off white, and purple) to find out its scope as cereal crop. Triglycerides, minerals and functional groups were determined through Gas chromatography, spectrophotometer and Fourier Transform Infrared (FTIR) spectrophotometer respectively. Results revealed variation among bulk densities, specific densities, percent empty spaces, and corresponding grain counts per 10 g of sample are useful in distinguishing brown, black, yellow, grey, green, off white, and purple wild adlay accessions. Specific density and grain count per 10 g sample was significantly related. No statistical relationship exists among the pronounced physical characteristics. Brown adlay expressed the highest protein, fat, and fiber contents 15.82%, 4.76% and 2.37% respectively. Protein, fat, ash, and fiber percent contents were found comparable to cultivated adlay. Spectrophotometric analysis revealed macro elements including phosphorus, potassium, calcium, and sodium in the range 0.3% - 2.2% and micro elements boron, iron, copper, zinc, and manganese in the range 1.6 mg/kg - 20.8 mg/kg. Gas chromatography showed polyunsaturated fatty acids (PUFA) constitute the primary fraction (39% ± 7.2) of wild adlay triglycerides. Linoleic and palmitic acids were present as prominent fatty acids, 43.5% ±1.4 and 26.3% ±1.4 respectively. Infra-red frequencies distinguished functional groups in narrow band and fingerprint region of protein in association with out of plane region leading to structural differences among adlay accessions. Comparison of major distinguishing vibrational frequencies among different flours indicated black adlay containing highest functional groups appeared promising for varietal development.

Five organotin(IV) derivatives (1–5) of general formula R3SnL and R2SnL2, where R = C4H9 {1, and 3}, CH3 {2 and 4}, C6H5 {5} and L represents 4-fluorophenoxyacetate ligand were synthesized by the condensation reaction of corresponding organotin(IV) chloride and sodium-4-fluorophenoxyaceate salt in dry chloroform under reflux condition. The elemental analysis has confirmed the expected composition of the complexes. The Δν values (less than 200 cm−1) calculated from FT-IR spectra revealed bridging/chelating bidentate coordination of the carboxylate ligand to the tin. The single crystal XRD analysis has shown polymeric chain structures for complexes 1 and 2 with bridging bidentate carboxylate ligand connecting tin atoms having trigonal bipyramidal geometry. In complex 3, the tin atom with chelating anisobidentate ligands adopted a highly distorted octahedral geometry. Quantum chemical studies have shown a good correlation between experimental and theoretically calculated geometric parameters. The Hirshfeld surface and fingerprint plots calculations have shown H…H interactions as the major intermolecular contacts present within the crystal structures of complexes 1–3. The experimental and simulated (1H and 13C) NMR spectra were found to be in good agreement. The in vitro enzyme inhibition {acetylcholinesterase (AChE), butyrylcholinesterase (BChE), monoamine oxidase B (MAO-B), alpha-glucosidase, dipeptidyl peptidase-4, cyclooxygenase (COX) and lipoxygenase (LOX)}, antioxidant [DPPH = 2,2-diphenyl-1-picrylhydrazyl and ABTS = 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid] and antileishmanial assays have shown dose dependent responses of the test compounds. Complexes have shown higher activities compared to the free ligand acid. Complexes were particularly more active acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) inhibitors, especially complex 3 (IC50 = 0.60 µg/mL) was even more potent than the standard drug Galantamine (IC50 = 2.82 µg/mL). MTT [MTT= (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide tetrazolium)] assay showed potent anticancer activity for complex 4 (IC50 = 12.54 ± 0.19 µg/mL), complex 5 (IC50 = 16.44 ± 0.17 µg/mL), and free 4-fluorophenoxyacetic acid (HL) (IC50 = 21.95 ± 0.09 µg/mL) among the tested compounds towards the brain cancer cell line (Malignant glioma U87). The nonmalignant human embryonic kidney HEK293 cells were found to be less vulnerable to the test compounds. In the antimicrobial assays, complexes 1 and 2 have shown activities higher than the standard drug Cefixime against C. albicans and P. aeruginosa, respectively.

Habenaria aitchisonii Reichb was analyzed in this research, including its chemical composition and its in vitro antioxidant, anti-inflammatory, acute oral toxicity, and antinociceptive activity. The chloroform and ethyl acetate fractions were found to be the most powerful based on in vitro antioxidant, anti-inflammatory, and analgesic assays. The acute oral toxicity of the crude methanolic extract was determined before in vivo studies. The acetic acid and formalin tests were used to measure the antinociceptive effect, and the potential mechanisms involved in antinociception were explored. The carrageenan-induced paw edema test was used to examine the immediate anti-inflammatory effect, and many phlogistic agents were used to determine the specific mechanism. Furthermore, for ex vivo activities, the mice were sacrificed, the forebrain was isolated, and the antioxidant levels of glutathione (GSH), superoxide dismutase (SOD), thiobarbituric acid reactive substances (TBARS) and catalase (CAT) were estimated using a UV spectrophotometer. No toxicity was seen at oral dosages up to 3,000 mg/kg. The antinociceptive impact was much higher than the standard drug. Both the inflammatory and neurogenic phases of the formalin experiment revealed an analgesic effect in the chloroform and ethyl acetate fractions. In carrageenan anti-inflammatory assays, the chloroform fraction (Ha.Chf) was the most potent fraction. We further studied the GC-MS of crude plant extract and found a total of 18 compounds. In the anti-inflammatory mechanism, it was observed that the Ha.Chf inhibits the COX-2 as well as 5-LOX pathways. The results exhibited that this species is a good source of phytocomponents like germacrone, which can be employed as a sustainable and natural therapeutic agent, supporting its traditional use in folk medicine for inflammatory conditions and pain.

Inflammation is a protective response to a variety of infectious agents. To develop a new anti-inflammatory drug, we explored a pharmacologically important thiazole scaffold in this study. In a multi-step synthetic approach, we synthesized seven new thiazole derivatives (5a–5g). Initially, we examined the in vitro anti-inflammatory potentials of our compounds using COX-1, COX-2, and 5-LOX enzyme assays. After in vitro confirmation, the potential compounds were subjected to in vivo analgesic and anti-inflammatory studies. The hot plate method was used for analgesia, and carrageenan-induced inflammation was also assayed. Overall, all our compounds proved to be potent inhibitors of COX-2 compared to celecoxib (IC50 0.05 μM), exhibiting IC50 values in the range of 0.76–9.01 μM .Compounds 5b, 5d, and 5e were dominant and selective COX-2 inhibitors with the lowest IC50 values and selectivity index (SI) values of 42, 112, and 124, respectively. Similarly, in the COX-1 assay, our compounds were relatively less potent but still encouraging. Standard aspirin exhibited an IC50 value of 15.32 μM. In the 5-LOX results, once again, compounds 5d and 5e were dominant with IC50 values of 23.08 and 38.46 μM, respectively. Standard zileuton exhibited an IC50 value of 11.00 μM. Based on the COX/LOX and SI potencies, the compounds 5d and 5e were subjected to in vivo analgesic and anti-inflammatory studies. Compounds 5d and 5e at concentrations of 5, 10, and 20 mg/kg body weight were significant in animal models. Furthermore, we explored the potential role of compounds 5d and 5e in various phlogistic agents. Similarly, both compounds 5d and 5e were also significantly potent in the anti-nociceptive assay. The molecular docking interactions of these two compounds with the target proteins of COX and LOX further strengthened their potential for use in COX/LOX pathway inhibitions.

Excessive and imbalance of free radicals within the body lead to inflammation. The objective of the current research work was to explore the anti-inflammatory and antioxidant potential of the isolated compounds from Habenaria digitata. In this study, the isolated phenolic compounds were investigated for in vitro and in vivo anti-inflammatory potential along with the antioxidant enzyme. The anti-inflammatory and antioxidant potential of the phenolic compounds was assayed via various enzymes like COX-1/2, 5-LOX and ABTS, DPPH, and H2O2 free radical enzyme inhibitory assay. These compounds were also explored for their in vivo antioxidant activity like examining SOD, CAT, GSH-Px, and MDA levels in the brain, heart, and liver. The anti-inflammatory potential was evaluated using the carrageenan-induced pleurisy model in mice. On the basis of initial screening of isolated compounds, the most potent compound was further evaluated for the anti-inflammatory mechanism. Furthermore, the molecular docking study was also performed for the potent compound. The phenolic compounds were isolated and identified by GC-MS/NMR analysis by comparing its spectra to the library spectra. The isolated phenolic compounds from H. digitata were 5-methylpyrimidine-24,4-diol (1), 3,5-dihydroxy-6-methyl-2,3-dihydropyran-4-one (2), 2-isopropyl-5-methylphenol (3), 3-methoxy-4-vinylphenol (4), and 2,6-dimethoxy-4-vinylphenol (5). In in vitro antioxidant assay, the most potent compound was compound 1 having IC50 values of 0.98, 0.90, and 5 μg/mL against ABTS, DPPH, and H2O2, respectively. Similarly, against COX1/2 and 5-LOX ,compound 1 was again the potent compound with IC50 values of 42.76, 10.70, and 7.40 μg/mL. Based on the in vitro results, compound 1 was further evaluated for in vivo antioxidant and anti-inflammatory potential. Findings of the study suggest that H. digitata contains active compounds with potential anti-inflammatory and antioxidant effects. These compounds could be screened as drug candidates for pharmaceutical research, targeting conditions associated with oxidative stress and inflammatory conditions in medicinal chemistry and support their ethnomedicinal use for inflammation and oxidative stress.

The strong ethnopharmacological utilization of Isodon rugosus Wall. Ex. Benth is evident in the treatment of several types of pain and inflammation, including toothache, earache, abdominal pain, gastric pain, and generalized body pain and inflammation. Based on this background, the antinociceptive effects of the crude extract, various fractions, and essential oil have been reported previously. In this research work, we isolate and characterize pure bioactive compounds from I. rugosus and evaluate possible mechanisms using various in vivo and in vitro models. The pure compounds were analyzed for analgesic and anti-inflammatory activities through various assays. The column chromatography of the chloroform fraction of I. rugosus led to the identification of two pure compounds, i.e., 1 and 2. Compound 1 demonstrated notable inhibition (62% writhing inhibition, 72.77% COX-2 inhibition, and 76.97% 5-LOX inhibition) and anti-inflammatory potential (>50% paw edema inhibition at various intervals). The possible mechanism involved in antinociception was considered primarily, a concept that has already been elucidated through the application of naloxone (an antagonist of opioid receptors). The involvement of adrenergic receptors was investigated using a hot plate model (an adrenergic receptor antagonist). The strong ethnomedicinal analgesic background of I. rugosus, supported by previous reports and current observations, leads to the conclusion that I. rugosus is a potential source of antinociceptive and anti-inflammatory bioactive compounds. It may be concluded from the results that the isolated analgesic compounds of I. rugosus may be a possible alternative remedy for pain and inflammation management with admirable efficacy and safety profiles.

Abstract Hyphaene thebaica fruits were used for the fabrication of spherical erbium oxide nanoparticles (HT-Er2O3 NPS) using a one-step simple bioreduction process. XRD pattern revealed a highly crystalline and pure phase with crystallite size of ~ 7.5 nm, whereas, the W–H plot revealed crystallite size of 11 nm. FTIR spectra revealed characteristic Er-O atomic vibrations in the fingerprint region. Bandgap was obtained as 5.25 eV using K-M function. The physicochemical and morphological nature was established using Raman spectroscopy, reflectance spectroscopy, SAED and HR-TEM. HT-Er2O3 NPS were further evaluated for antidiabetic potential in mice using in-vivo and in-vitro bioassays. The synthesized HT-Er2O3 NPS were screened for in vitro anti-diabetic potentials against α-glucosidase enzyme and α-amylase enzyme and their antioxidant potential was evaluated using DPPH free radical assay. A dose dependent inhibition was obtained against α-glucosidase (IC50 12 μg/mL) and α-amylase (IC50 78 μg/mL) while good DPPH free radical scavenging potential (IC50 78 μg mL−1) is reported. At 1000 μg/mL, the HT-Er2O3 NPS revealed 90.30% and 92.30% inhibition of α-amylase and α-glucosidase enzymes. HT-Er2O3 NPs treated groups were observed to have better glycemic control in diabetic animals (503.66 ± 5.92*** on day 0 and 185.66 ± 2.60*** on day 21) when compared with positive control glibenclamide treated group. Further, HT-Er2O3 NPS therapy for 21 days caused a considerable effect on serum total lipids, cholesterol, triglycerides, HDL and LDL as compared to untreated diabetic group. In conclusion, our preliminary findings on HT-Er2O3 NPS revealed considerable antidiabetic potential and thus can be an effective candidate for controlling the post-prandial hyperglycemia. However, further studies are encouraged especially taking into consideration the toxicity aspects of the nanomaterial.

Abstract Aim The study was planned to investigate the phytochemicals, antidiabetic and antioxidant studies of A. consanguineum. Methods The preliminary studies were performed on crude extract and different solvent fractions. Based on the potency, the chloroform fraction was semi-purified to phyto-fractions CHF-1 – 5. Furthermore, CHF-3 was subjected to isolation of pure compounds using column chromatography. The α-glucosidase, α-amylase and antioxidant assays (DPPH, ABTS, H2O2) were performed on all samples. The in-vivo experiments on compounds 1 and 2 were also performed using oral glucose tolerance test. Docking studies were performed on α-glucosidase and α-amylase targets. Results Among all fractions, the chloroform fraction exhibited excellent activities profile giving IC50 values of 824, 55, 117, 58 and 85 μg/ml against α-glucosidase, α-amylase, DPPH, ABTS and H2O2 targets respectively. Among the five semi-purified chloroform phyto-fractions (CHF-1-5), CHF-3 was the leading fraction in activities giving IC50 values of 85.54, 61.19 and 26.58 μg/ml against α-glucosidase, α-amylase and DPPH respectively. Based on the overall potency and physical amount of CHF-3, it was subjected to purification to get compounds 1 and 2. The two compounds were also found potent in in-vitro activities. The observed IC50 values for compound 1 were 7.93, 28.01 and 6.19 μg/ml against α-glucosidase, α-amylase and DPPH respectively. Similarly, the compound 2 exhibited IC50 of 14.63, 24.82 and 7.654 μg/ml against α-glucosidase, α-amylase and DPPH respectively. Compounds 1 and 2 were potent in decreasing the blood glucose levels in experimental animals. Compounds 1 and 2 also showed interactions with the respective enzymes with molecular docking. Conclusions We can conclude that A. Consanguineum is a rich source of natural antidiabetic agents. Bioguided isolation of compound 1 and 2 showed potential inhibitions in all tested in-vitro antidiabetic targets. Further, both the compounds were also able to decrease the blood glucose levels in experimental animals.

Diabetes mellitus (DM) is a metabolic complication and can pose a serious challenge to human health. DM is the main cause of many life-threatening diseases. Researchers of natural products have been continuously engaged in treating vital diseases in an economical and efficient way. In this research, we extensively used phytosteroids from Notholirion thomsonianum (Royle) Stapf for the treatment of DM. The structures of phytosteroids NtSt01 and NtSt02 were confirmed with gas chromatography–mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) analyses. Through in vitro studies including α-glucosidase, α-amylase, and DPPH assays, compound NtSt01 was found to be comparatively potent. An elevated dose of compound NtSt01 was also found to be safe in an experimental study on rats. With a dose of 1.0 mg/kg of NtSt01, the effect on blood glucose levels in rats was observed to be 519 ± 3.98, 413 ± 1.87, 325 ± 1.62, 219 ± 2.87, and 116 ± 1.33 mg/dL on the 1st, 7th, 14th, 21st, and 28th, days, respectively. The in vivo results were compared with those of glibenclamide, which reduced the blood glucose level to 107 ± 2.33 mg/dL on the 28th day. On the 28th day of NtSt01 administration, the average weights of the rats and vital organs (liver, kidney, pancreas, and heart) remained healthy, with a slight increase. The biochemical parameters of the blood, i.e., serum creatinine, blood urea, serum bilirubin, SGPT (or ALT), and serum alkaline phosphatase, of rats treated with NtSt01 remained in the normal ranges. Similarly, the serum cholesterol, triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels also remained within the standard ranges. It is obvious from our overall results that the phytosteroids (specifically NtSt01) had an efficient therapeutic effect on the blood glucose level, protection of vital organs, and blood biochemistry.

Abstract Background Natural phenolic compounds and Phenolics-rich medicinal plants are also of great interest in the management of diabetes. The current study was aimed to analyze phenolics in P. hydropiepr L extracts via HPLC-DAD analysis and assess their anti-diabetic potentials using in-vitro and in-silico approaches. Methods Plant crude methanolic extract (Ph.Cme) was evaluated for the presence of phenolic compounds using HPLC-DAD analysis. Subsequently, samples including crude (Ph.Cr), hexane (Ph.Hex), chloroform (Ph.Chf), ethyl acetate (Ph.EtAc), butanol (Ph.Bt), aqueous (Ph.Aq) and saponins (Ph.Sp) were tested for α-glucsidase and α-amylase inhibitory potentials and identified compounds were docked against these target enzymes using Molecular Operating Environment (MOE) software. Fractions were also analyzed for the nutritional contents and acute toxicity was performed in animals. Results In HPLC-DAD analysis of Ph.Cme, 24 compounds were indentfied and quantified. Among these, Kaemferol-3-(p-coumaroyl-diglucoside)-7-glucoside (275.4 mg g− 1), p-Coumaroylhexose-4-hexoside (96.5 mg g− 1), Quercetin-3-glucoronide (76.0 mg g− 1), 4-Caffeoylquinic acid (58.1 mg g− 1), Quercetin (57.9 mg g− 1), 5,7,3′-Trihydroxy-3,6,4′,5′-tetramethoxyflavone (55.5 mg g− 1), 5-Feruloylquinic acid (45.8 mg g− 1), Cyanidin-3-glucoside (26.8 mg g− 1), Delphinidin-3-glucoside (24 mg g− 1), Quercetin-3-hexoside (20.7 mg g− 1) were highly abundant compounds. In α-glucosidase inhibition assay, Ph.Sp were most effective with IC50 value of 100 μg mL-1. Likewise in α-amylase inhibition assay, Ph.Chf, Ph.Sp and Ph.Cme were most potent fractions displayed IC50 values of 90, 100 and 200 μg mL-1 respectively. Docking with the α-glucosidase enzyme revealed top ranked conformations for majority of the compounds with Kaemferol-3-(p-coumaroyl-diglucoside)-7-glucoside as the most active compound with docking score of − 19.80899, forming 14 hydrogen bonds, two pi-H and two pi-pi linkages with the Tyr 71, Phe 158, Phe 177, Gln 181, Arg 212, Asp 214, Glu 276, Phe 300, Val 303, Tyr 344, Asp 349, Gln 350, Arg 439, and Asp 408 residues of the enzyme. Likewise, docking with α-amylase revealed that most of the compounds are well accommodated in the active site residues (Trp 59, Tyr 62, Thr 163, Leu 165, Arg 195, Asp 197, Glu 240, Asp 300, His 305, Asp 356) of the enzyme and Cyanidin-3-rutinoside displayed most active compound with docking score of − 15.03757. Conclusions Phytochemical studies revealed the presence of highly valuable phenolic compounds, which might be responsible for the anti-diabetic potentials of the plant samples.

In this study, the newly synthesized compound (Succ-5) was analyzed through spectral methods, seen for potential receptor targets via molecular docking, and pre-clinically evaluated for therapeutic effects and safety profile using biochemical and histopathological techniques. The biochemical analysis included assessment of cardiac biomarkers, hepatic enzymes, and lipid profiles, while histopathology included evaluation of cardiac and liver tissues. The toxic dose was determined pre-clinically, followed by dividing albino rats into five treatment groups (each having n = 6). The control group received oral saline for eight days. The 5-FU (5-Fluorouracil) group received oral saline for 8 days and 5-FU (150 mg/kg I.P.) on day 5. The atenolol group was administered with atenolol (20 mg/kg) for 8 days and 5-FU (150 mg/kg I.P.) on day 5. Two groups of rats were administered with the test compound (Succ-5) at doses of 5 mg/kg I.P and 10 mg/kg I.P (for 8-days), followed by 5-FU (150 mg/kg I.P.) on day 5. Elevated serum levels of CK-MB (creatinine kinase myocardial band), cTnI (troponin I), LDH (lactate dehydrogenase), lipid profile, and selected liver enzymes including ALP (alkaline phosphatase), ALT (alanine transaminase), AST (aspartate aminotransferase), BT (bilirubin total) and BD (direct bilirubin) were associated with 5-FU toxicity. After administration of the test compound at the mentioned doses, these biomarkers significantly decreased. Likewise, histological examination revealed 5-FU damaged the heart and hepatic tissues, which were also considerably recovered following administration of the test compound. Immunohistochemistry of heart tissue also revealed the low expression of COX-2 and TNF-α in Succ-5 treated groups compared to toxic group. Dose-response evaluation showed that a dose of 10 mg/kg provided better results than 5 mg/kg. The analysis of binding energy values computed via docking simulations showed that Succ-5 interacts with the human beta2-adrenergic G protein-coupled receptor with a slightly stronger affinity than calcium channel T-type. In conclusion, the histological and biochemical findings revealed that the test compound had significant cardioprotective, hepatoprotective, and lipolytic effects in the 5-FU-induced toxicity.

Abstract Background Edible oils have proven health benefits in the prevention and treatment of various disorders since the establishment of human era. This study was aimed to appraise neuropharmacological studies on the commonly used edible oils including Cinnamomum verum (CV), Zingiber officinale (ZO) and Cuminum cyminum (CC). Methods The oils were analyzed via GC-MS for identifications of bioactive compounds. Anti-radicals capacity of the oils were evaluated via 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radicals scavenging assays. The samples were also tested against two important acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) which are among the important drug targets in Alzheimer’s disease. Lineweaver-Burk plots were constructed for enzyme inhibition studies which correspond to velocity of enzymes (Vmax) against the reciprocal of substrate concentration (K m ) in the presence of test samples and control drugs following Michaelis-Menten kinetics. Docking studies on AChE target were also carried out using Molecular Operating Environment (MOE 2016.0802) software. Results (Gas chromatography-mass spectrometry GC-MS) analysis revealed the presence of thirty-four compounds in Cinnamon oil (Cv.Eo), fourteen in ginger oil (Zo.Eo) and fifty-six in cumin oil (Cc.Eo). In the antioxidant assays, Cv.Eo, Zo.Eo and Cc.Eo exhibited IC50 values of 85, 121, 280 μg/ml sequentially against DPPH radicals. Whereas, in ABTS assay, Cv.Eo, Zo.Eo and Cc.Eo showed considerable anti-radicals potentials with IC50 values of 93, 77 and 271 μg/ml respectively. Furthermore, Cv.Eo was highly active against AChE enzyme with IC50 of 21 μg/ml. Zo.Eo and Cc.Eo exhibited considerable inhibitory activities against AChE with IC50 values of 88 and 198 μg/ml respectively. In BChE assay, Cv.Eo, Zo.Eo and Cc.Eo exhibited IC50 values of 106, 101 and 37 μg/ml respectively. Our results revealed that these oils possess considerable antioxidant and cholinesterase inhibitory potentials. As functional foods these oils can be effective remedy for the prevention and management of neurological disorders including AD. Synergistic effect of all the identified compounds was determined via binding energy values computed through docking simulations. Binding orientations showed that all the compounds interact with amino acid residues present in the peripheral anionic site (PAS) and catalytic anionic site (CAS) amino acid residues, oxyanion hole and acyl pocket via π-π stacking interactions and hydrogen bond interactions.

Abstract Background Diabetes mellitus is a common disease effecting the lifestyles of majority world population. In this research work, we have embarked the potential role of crude extracts and isolated compounds of Notholirion thomsonianum for the management diabetes mellitus. Methods The crude extracts of N. thomsonianum were initially evaluated for α-glucosidase, α-amylase and antioxidant activities. The compounds were isolated from the activity based potent solvent fraction. The structures of isolated compounds were confirmed with NMR and MS analyses. The isolated compounds were tested for α-glucosidase, α-amylase, protein tyrosine phosphatase 1B (PTP1B) and DPPH activities. The molecular docking studies were carried out to find the binding interactions of isolated compounds for α-glucosidase, α-amylase and PTP1B. Results Initially, we screened out crude extracts and subfractions of N. thomsonianum against different in-vitro targets. Among all, Nt.EtAc was observed a potent fraction among all giving IC50 values of 67, 70,

Oxidative stress (OS) disrupts the chemical integrity of macromolecules and increases the risk of neurodegenerative diseases. Fisetin is a flavonoid that exhibits potent antioxidant properties and protects the cells against OS. We have viewed the NCBI database, PubMed, Science Direct (Elsevier), Springer-Nature, ResearchGate, and Google Scholar databases to search and collect relevant articles during the preparation of this review. The search keywords are OS, neurodegenerative diseases, fisetin, etc. High level of ROS in the brain tissue decreases ATP levels, and mitochondrial membrane potential and induces lipid peroxidation, chronic inflammation, DNA damage, and apoptosis. The subsequent results are various neuronal diseases. Fisetin is a polyphenolic compound, commonly present in dietary ingredients. The antioxidant properties of this flavonoid diminish oxidative stress, ROS production, neurotoxicity, neuro-inflammation, and neurological disorders. Moreover, it maintains the redox profiles, and mitochondrial functions and inhibits NO production. At the molecular level, fisetin regulates the activity of PI3K/Akt, Nrf2, NF-κB, protein kinase C, and MAPK pathways to prevent OS, inflammatory response, and cytotoxicity. The antioxidant properties of fisetin protect the neural cells from inflammation and apoptotic degeneration. Thus, it can be used in the prevention of neurodegenerative disorders.

Suboptimal antibiotics use and the development of antibiotic resistance is a universal calamity. The theoretical model of therapeutic efficacy correlates quality use of antibiotics with healthcare practitioners’ understanding of antibiotic use and resistance. Keeping this phenomenon in mind, we aimed to evaluate hospital pharmacists’ understanding of antibiotic use and resistance at a public healthcare institute in Quetta city, Pakistan. This was a qualitative study that employed a semi-structured interview guide for data extraction. The phenomenology-based approach commissioned in-depth, face-to-face interviews with hospital pharmacists stationed at the surgical unit of Sandeman Provincial Hospital, Quetta. The interviews were audio taped followed by transcribed verbatim and were then analyzed for thematic contents by the standard content analysis framework. Although the saturation was reached after the 10th interview, we conducted two additional interviews for definite validation. Content analysis revealed five major themes: (1) Defining antibiotics, quality use of antibiotics and resistance, (2) antibiotic use: awareness and concern, (3) antimicrobial resistance: awareness and concern, (4) responding to antibiotic use and resistance, and (5) barriers to quality use of antibiotics and prevention of antibiotic resistance. The knowledge of quality use of antibiotics and resistance was promising, and the respondents were eager to address the drastic situation. The respondents were aware of the critical situation and provided valuable insights that can offer valued input while promoting the quality use of antibiotics in a developing country. The current study managed to identify an adequate understanding of antibiotic use and resistance among hospital pharmacists. Additionally, prospective concerns and possible predictors of antibiotic resistance were also highlighted. The current findings must be disseminated to the policymakers and prescribers to take prompt restorative actions to address antibiotic use and the development of antibiotic resistance in a developing country like Pakistan.

Abstract Background According to the recent global cancer statistics, breast cancer is the leading cause of deaths among women with 2.3 million new cases globally. Likewise, cervical cancer is also among the leading causes of mortality among women. Polygonum hydropiper is traditionally known for its cytotoxic effects and several bioactive cytotoxic compounds were isolated from it. This study was aimed to isolate potential anticancer compounds from its most potent fractions and evaluate their anticancer potentials. Methods Based on our earlier studies, active fractions including chloroform and ethyl acetate were subjected to column chromatography for isolation of compounds. Chemical structures of isolated compounds were confirmed via 1H NMR, 13C NMR, mass spectrometry. Purified compounds were tested for cytotoxicity against breast cancer cells (MCF-7), cervical cancer cells (HeLA) and NIH/3T3 fibroblasts cells cultures using MTT assy. Anti-angiogenic potentials of isolated compounds were evaluated via chorioallantoic membrane assay. Anti-tumor studies were done using Agrobacterium tumefaciens induced potato tumor assay. Furthermore, to understand the binding modes of Isolated compounds, molecular docking was performed against EGFR, HER2 and VEGFR using MOE as docking software. Results Two bioactive compounds PH-1 (4-methyl-5-oxo-tetrahydrofuran-3-yl acetate) and PH-2 (methyl 4-hydroxy-3-methoxybenzoate) were purified from the active fractions. In cytotoxicity studies, PH-1 exhibited highest cytotoxicity against HeLA cells with 87.50% lethality at 1 mgmL−1 concentration and LD50 of 60 µgmL−1. Likewise, PH-2 showed 82.33% cytotoxicity against HeLA cells with LD50 of 160 µgmL−1. Similarly, PH-1 and PH-2 exhibited LD50 of 170 and 380 µgmL−1 respectively. Moreover, PH-1 and PH-2 were also very potent cytotoxic compounds against NIH/3T3 cells with 81.45 and 85.55% cytotoxicity at 1 mgL−1 concentration and LD50 of 140 and 58 µgL−1 respectively. Isolated compounds exhibited considerable anti-angiogenic potentials with IC50 of 340 and 500 µgL−1 respectively for PH-1 and PH-2. In anti-tumor assay, PH-1 and PH-2 exhibited 81.15 and 76.09% inhibitions with LD50 of 340 and 550 µgL−1 respectively. Both compounds selectively binds with EGFR and HER2 receptors with low binding energies. Both compounds exhibited stronger interactions with VEGFR through binding pocket residues Lys868, Val916 and Asp1046. Conclusions Both compounds cause considerable cytotoxicity against cancer cells. The anti-angiogenic and anti-tumor results suggests additional tumor suppressive properties. Docking analysis suggests that these compound not only has the ability to bind to EGFR and HER2 but also equally binds to VEGFR and may act as potential anti-angiogenic agents.

The current research was intended to establish the impact of Silibinin nanoparticles (SB-APSP) produced by the antisolvent precipitation with a syringe pump (APSP). The in-vivo bioavailability and hepatoprotective activity of SB-APSP were evaluated in experimental animals. To determine the pharmacokinetic parameters, silibinin and its nanoparticles were given orally to rabbits at a dose of 50 mg/Kg body weight. Blood samples were drawn at different time intervals and were analyzed using HPLC. The bioavailability of un processed silibinin was lower as compared to silibinin nanoparticles (3.45 ± 0.07 and 23.76 ± 0.07 µg/mL respectively). The AUC and Cmax of SB-APSP were found to be 15.56 and 6.88 folds greater for nanoparticles when compared to silibinin. Hepatoprotective study in Male Sprague Dawley rats revealed that SB-APSP provide better recovery of the damaged liver cell induced by CCl4. Histopathology of the liver revealed that SB-APSP provide better protection to the liver cells from the damage induced by CCl4 and maintained the hepatic lobule histopathology more efficiently. It was concluded that the SB-APSP can more effectively protect the liver in experimental animals in a far better way compared to the un-processed Silibinin and could be used as an efficient hepatoprotective agent. Keywords: Silibinin, Pharmacokinetic parameters, Carbon tetrachloride, Hepatoprotective activity

BackgroundType 2 Diabetes-related medication errors are frequently reported from the hospitals and consequently are of major concern. However, such reports are insufficient when developing healthcare settings are pursued in literature. Keeping this inadequacy in mind, we therefore aimed to explore physicians' perceptions, experiences and expectations of medication errors when managing patients with Type 2 Diabetes Mellitus.MethodsA qualitative design was adopted. By using a semi-structured interview guide through the phenomenology-based approach, in-depth, face-to-face interviews were conducted. Physicians practicing at the medicine ward of Sandeman Provincial Hospital, Quetta, were purposively approached for the study. All interviews were audio-taped, transcribed verbatim, and were then analyzed for thematic contents by the standard content analysis framework.ResultsAlthough the saturation was reached at the 13th interview, we conducted additional two interviews to ensure the saturation. Fifteen physicians were interviewed, and thematic content analysis revealed six themes and nine subthemes. Mixed conceptualization and characterization of medication errors were identified. Medication errors were encountered by all physicians however poor understanding of the system, deficiency of logistics and materials were rated as barriers in reporting medication errors. Among contributors of medication errors, physicians themselves as well as dispensing and patient-related factors were identified. Physicians suggested targeted training sessions on medication error-related guidelines and reporting system. Parallel, establishment of an independent unit, involving the pharmacists, and strict supervision of paramedics to minimize medication errors was also acknowledged during data analysis.ConclusionWith a longer life expectancy and a trend of growing population, the incidences of medication errors are also expected to increase. Our study highlighted prescribing, dispensing and administration phases as contributing factors of medication errors. Although, physicians had poor understanding of medication errors and reporting system, they believed getting insights on guidelines and reporting system is essential. A review of admission and discharge reconciliation must be prioritized and a culture of teamwork, communication and learning from mistakes is needed.

Cancer therapies are associated with various challenges including the emergence of multidrug resistant tumors, toxicological issues, severe side effects, and economic burden. To counteract these effects, natural products as substitutes and adjuvant therapies have received considerable attention owing to their safety, efficacy, and economic aspects. Various preclinical and clinical studies revealed that natural products and their combinations with chemotherapeutics mediate their anticancer effects via modulation of various signaling pathways implicated in promoting apoptosis, inhibiting excessive cellular proliferation, and mobilizing the immune system. Several lead phytochemicals including curcumin, resveratrol, quercetin, and cannabinoids synergistically act with cancer chemotherapeutics reducing cell proliferation and inducing apoptosis and cell cycle arrest. However, clinical studies on the subject matter are limited and need further extensive studies. It has been observed that patients undergoing chemotherapy use alternative therapies to ameliorate the symptoms associated with the use of chemotherapeutic agents. Nevertheless, some of the patients inform their physicians regarding herbal medicine during chemotherapy while others do not, and even most of the patients do not know the composition of herbal medicine they consume during chemotherapy. Herbal interactions with chemotherapeutics are associated with both beneficial and harmful aspects, but the beneficial aspect overweighs the harmful ones in terms of controlling the symptoms associated with the chemotherapy. Nonetheless, a large number of herbal medicines have been demonstrated to have synergistic effect with chemotherapy and alleviate the side effects of chemotherapeutic agents. The concomitant use of the majority of herbal medicines with chemotherapy has been demonstrated to be beneficial in multiple malignant tumors like cancer of blood, lungs, kidneys, liver, skin, and gastrointestinal tract. However, herbal medicines which possess positive interaction and improve the quality of life of patients should be sorted out and integrated with the chemotherapy. There should be a quality control system for the appraisal of herbal medicine, and there should also be an appropriate system of patient-doctor communication to counsel the patients regarding the beneficial and deleterious effects of the herbal medicine in combination with chemotherapy.

BackgroundQuality of Life (QoL) and its determinants are significant in all stages of life, including pregnancy. The physical and emotional changes during pregnancy affect the QoL of pregnant women, affecting both maternal and infant health. Hence, assessing the QoL of pregnant women is gaining interest in literature. We, therefore, aimed to describe the QoL of pregnant women during physiological pregnancy and to identify its associated predictors in women attending a public healthcare institute of Quetta city, Pakistan.MethodsA cross-sectional study was conducted at the Obstetrics and Gynecology Department of Sandeman Provincial Hospital Quetta city, Pakistan. The respondents were asked to answer the Urdu (lingua franca of Pakistan) version of the Quality of Life Questionnaire for Physiological Pregnancy. Data were coded and analyzed by SPPS v 21. The Kolmogorov–Smirnov test was used to establish normality of the data and non-parametric tests were used accordingly. Quality of Life was assessed as proposed by the developers. The Chi-square test was used to identify significant associations and linear regression was used to identify the predictors of QoL. For all analyses, p < 0.05 was taken significantly.ResultsFour hundred and three pregnant women participated in the study with a response rate of 98%. The mean QoL score was 19.85 ± 4.89 indicating very good QoL in the current cohort. The Chi-Square analysis reported a significant association between age, education, occupation, income, marital status, and trimester. Education was reported as a positive predictor for QoL (p = 0.006, β = 2.157). On the other hand, trimester was reported as a negative predictor of QoL (p = 0.013, β = −1.123).ConclusionImproving the QoL among pregnant women requires better identification of their difficulties and guidance. The current study highlighted educational status and trimester as the predictors of QoL in pregnant women. Health care professionals and policymakers should consider the identified factors while designing therapeutic plans and interventions for pregnant women.

Inflammation, being a well-known and complex pathological condition, is always a challenge to the human health. This research work was designed for a rationale-based anti-inflammatory study on β-ketoester derivatives of N-ary succinimides. The compounds (A–D) were synthesized by organocatalytic Michael addition. The compounds were initially screened for in vitro 5-lipoxygenase (5-LOX) and cyclooxygenase (COX-2) assays. For the in vivo activity, carrageenan-induced paw edema and arachidonic acid-induced ear edema tests were used. Furthermore, different in vivo pathways such as prostaglandins E2, histamine, leukotriene, and bradykinin were studied. The results were supported with molecular docking studies. Among the compounds, D (ethyl 1-(1-benzyl-2,5-dioxopyrrolidin-3-yl)-2-oxocyclohexane-1-carboxylate) at a concentration of 1000 μg/ml showed significant inhibitory effects of 83.67% and 78.12% against COX-2 and 5-LOX in comparison to celecoxib and zileuton, respectively. Similarly, compound D also showed excellent in vivo anti-inflammatory potential. Amongst all the compounds, D demonstrated excellent (55.92 ± 2.95%) anti-inflammatory potential at maximum tested dose (100 mg/kg) which accomplished the highest significance at 4 h following the carrageenan insertion and stayed considerable (∗∗∗P

The convenient and highly compliant route for the delivery of active pharmaceutical ingredients is the tablet. A versatile platform of tablets is available for the delivery of therapeutic agents to the gastrointestinal tract. This study aimed to prepare gastro retentive drug delivery floating tablets of silymarin to improve its oral bioavailability and solubility. Hydroxypropyl methylcellulose (HPMCK4M and HPMCK15), Carbopol 934p and sodium bicarbonate were used as a matrix, floating enhancer and gas generating agent, respectively. The prepared tablets were evaluated for physicochemical parameters such as hardness, weight variation, friability, floating properties (floating lag time, total floating time), drug content, stability study, in vitro drug release, in vivo floating behavior and in vivo pharmacokinetics. The drug–polymer interaction was studied by Differential Scanning Calorimetry (DSC) thermal analysis and Fourier transform infrared (FTIR). The floating lag time of the formulation was within the prescribed limit (12 h. The dissolution can be described by zero-order kinetics (r2 = 0.979), with anomalous diffusion as the release mechanism (n = 0.65). An in vivo pharmacokinetic study showed that Cmax and AUC were increased by up to two times in comparison with the conventional dosage form. An in vivo imaging study showed that the tablet was present in the stomach for 12 h. It can be concluded from this study that the combined matrix system containing hydrophobic and hydrophilic polymers min imized the burst release of the drug from the tablet and achieved a drug release by zero-order kinetics, which is practically difficult with only a hydrophilic matrix. An in vivo pharmacokinetic study elaborated that the bioavailability and solubility of silymarin were improved with an increased mean residence time.

Diabetes mellitus (DM) is counted among one of the leading challenges in the recent era, and it is a life-threatening disorder. Compound 4-hydroxy 3-methoxy phenylacetone (compound 1) was previously isolated from Polygonum aviculare. This compound was reacted with N-benzylmaleimide to synthesize the targeted compound 3. The purpose of this research is to exhibit our developed compound 3’s ability to concurrently inhibit many targets that are responsible for hyperglycemia. Compound 3 was capable of inhibiting α-amylase, α-glucosidase, and protein tyrosine phosphatase 1 B. Even so, outstanding in vitro inhibition was shown by the compound against dipeptidyl peptidase-4 (DPP-4) with an IC50 value of 0.07 µM. Additionally, by using DPPH in the antioxidant activity, it exhibited good antioxidant potential. Similarly, in the in vivo activity, the experimental mice proved to be safe by treatment with compound 3. After 21 days of examination, the compound 3 activity pattern was found to be effective in experimental mice. Compound 3 decreased the excess peak of total triglycerides, total cholesterol, AST, ALT, ALP, LDL, BUN, and creatinine in the STZ-induced diabetic mice. Likewise, the histopathology of the kidneys, liver, and pancreas of the treated animals was also evaluated. Overall, the succinimde moiety, such as compound 3, can affect several targets simultaneously, and, finally, we were successful in synthesizing a multi-targeted preclinical therapy.

Diabetes mellitus (DM) is a metabolic disorder majorly arising from the pathophysiology of the pancreas manifested as a decline in the insulin production or the tissue’s resistance to the insulin. In this research, we have rationally designed and synthesized new succinimide–thiazolidinedione hybrids for the management of DM. In a multistep reaction, we were able to synthesize five new derivatives (10a–e). All the compounds were new containing a different substitution pattern on the N-atom of the succinimide ring. Initially, all the compounds were tested against the in vitro α-glucosidase, α-amylase, PTP1B, and DPP4 targets. In all of these targets, the compound 10d was observed to be the most potential antidiabetic agent. Based on this, the antidiabetic activity of the compound 10d was further investigated in experimental animals, which overall gave us encouraging results. The molecular docking studies of the compound 10d was also performed against the target enzymes α-glucosidase, α-amylase, PTP1B, and DPP4 using MOE. Overall, we observed that we have explored a new class of compounds as potential antidiabetic agents.

Objective: The research was designed to study the different epidemiological and PCR-based identification of Vibrio cholera. Method: The cross sectional study was performed in Center for Advanced Studies in Vaccinology and Biotechnology, University of Balochistan, Quetta from January 5, 2019 till December 6, 2019. Fecal / rectal swab samples were taken with a history of untreated severe (rice water) diarrhea of less than 12 hours duration. Total 444 stool samples were collected from suspected cholera patients at different hospitals of Balochistan. Isolates were examined and identified on the basis of colony characters on TCBS agar. susppected colonies were subjected to gram staining, various biochemical tests and PCR base identification. Results: The result shows that 7.43 % were V.cholerae positive while 92.56% were found negative. The rates of incidence was highest in individuals in 1-20 years old patients as compared to other age group patients. The gender wise distribution of cholera infection was found high in male (4.05%) as compared to female patients (3.37%). The percentage of cholera infection was high in Baluch (4.05%) race as compared to other races of Baluchistan. The status wise distribution showed that lower class (4.05%) was more affected as compared to other classes of Balochistan. Literacy and illiteracy wise distribution showed that the illiterate patients (5.85%) were more affected. The incidence of cholera infection was more in summer (4.27%) and spring (1.80%) seasons as compared to other seasons of Balochistan. Continuous...

Background: To identify and address the potential overuse of antibiotics, it is important to ascertain the prescribing practices of physicians. We, therefore, conducted this prescription analysis to document URTI-specific antibiotic prescription frequency in a public primary healthcare setting of Quetta city, Pakistan.Methods: A retrospective record review was conducted of all prescriptions for URTIs in Combined Military Hospital, Quetta from 1 March to 31st May 2021. The Mann-Whitney U and Jonckheere–Terpstra test was used to evaluate the association between the tendencies of a different group of prescribers. p-value of

Brucella suis, one of the causative agents of brucellosis, is Gram-negative intracellular bacteria that may be found all over the globe and it is a significant facultative zoonotic pathogen found in livestock. It may adapt to a phagocytic environment, reproduce, and develop resistance to harmful environments inside host cells, which is a crucial part of the Brucella life cycle making it a worldwide menace. The molecular underpinnings of Brucella pathogenicity have been substantially elucidated due to comprehensive methods such as proteomics. Therefore, we aim to explore the complete Brucella suis proteome to prioritize the novel proteins as drug targets via subtractive proteo-genomics analysis, an effort to conjecture the existence of distinct pathways in the development of brucellosis. Consequently, 38 unique metabolic pathways having 503 proteins were observed while among these 503 proteins, the non-homologs (n = 421), essential (n = 350), drug-like (n = 114), virulence (n = 45), resistance (n = 42), and unique to pathogen proteins were retrieved from Brucella suis. The applied subsequent hierarchical shortlisting resulted in a protein, i.e., isocitrate lyase, that may act as potential drug target, which was finalized after the extensive literature survey. The interacting partners for these shortlisted drug targets were identified through the STRING database. Moreover, structure-based studies were also performed on isocitrate lyase to further analyze its function. For that purpose, ~18,000 ZINC compounds were screened to identify new potent drug candidates against isocitrate lyase for brucellosis. It resulted in the shortlisting of six compounds, i.e., ZINC95543764, ZINC02688148, ZINC20115475, ZINC04232055, ZINC04231816, and ZINC04259566 that potentially inhibit isocitrate lyase. However, the ADMET profiling showed that all compounds fulfill ADMET properties except for ZINC20115475 showing positive Ames activity; whereas, ZINC02688148, ZINC04259566, ZINC04232055, and ZINC04231816 showed hepatoxicity while all compounds were observed to have no skin sensitization. In light of these parameters, we recommend ZINC95543764 compound for further experimental studies. According to the present research, which uses subtractive genomics, proteins that might serve as therapeutic targets and potential lead options for eradicating brucellosis have been narrowed down.

Plants’ bioactives are well-known safe drugs for vital diseases. Flavones and Flavonoid-rich dietary supplements are known to exhibit neuroprotective potential. In this study, we isolated a flavone 2-(3,4-dimethoxyphenyl)-3,7-dihydroxy-4H-chromen-4-one from Notholirion thomsonianum and it was evaluated against various targets of the oxidative stress-related neurological disorders. The compound showed excellent acetyl and butyrylcholinesterase inhibitions in its profile, giving IC50 values of 1.37 and 0.95 μM, respectively. Similarly, in in-vitro MAO-B assay, our flavone exhibited an IC50 value of 0.14 μM in comparison to the standard safinamide (IC50 0.025 μM). In in-vitro anti-inflammatory assay, our isolated compound exhibited IC50 values of 7.09, 0.38 and 0.84 μM against COX-1, COX-2 and 5-LOX, respectively. The COX-2 selectivity (SI) of the compound was 18.70. The compound was found safe in animals and was very effective in carrageenan-induced inflammation. Due to the polar groups in the structure, a very excellent antioxidant profile was observed in both in-vitro and in-vivo models. The compound was docked into the target proteins of the respective activities and the binding energies confirmed the potency of our compound. Furthermore, absorption, distribution, metabolism, excretion, and toxicity (ADMET) results showed that the isolated flavone has a good GIT absorption ability and comes with no hepatic and cardiotoxicity. In addition, the skin sensitization test, in-vitro human cell line activation test (h-CLAT) and KeratinoSens have revealed that isolated flavone is not skin sensitive with a confidence score of 59.6% and 91.6%. Herein, we have isolated a natural flavone with an effective profile against Alzheimer’s, inflammation and oxidative stress. The exploration of this natural flavone will provide a baseline for future research in the field of drug development.

Abstract Background Bergenia ciliata is a medicinal plant used for the treatment of diarrhea, vomiting, fever, cough, diabetes, cancer, pulmonary disorders and wound healing. Methods In this study, Bergenia ciliata crude extract, subfractions, and isolated compounds were evaluated for their antioxidant and anticholinesterase potential. The free radical scavenging capacities of the extracts determined using DPPH and ABTS assays. The anticholinesterase potentials were determined using acetylcholine esterase and butyryl choline esterase enzymes. To determine the phytochemical composition, the extracts were subjected to HPLC analysis and silica gel column isolation. Based on HPLC fingerprinting results, the ethyl acetate fraction was found to have more bioactive compounds and was therefore subjected to silica gel column isolation. As a result, three compounds; pyrogallol, rutin, and morin were isolated in the pure state. The structures of the isolated compounds were elucidated using spectroscopic techniques like 1H-NMR, IR and UV-Visible. Results The crude extract showed maximum anticholinesterase (acetylcholinesterase = 90.22 ± 1.15% and butyrylcholinesterase = 88.22 ± 0.71%) and free radical scavenging (87.37 ± 2.45 and 83.50 ± 0.70% respectively against DPPH and ABTS radicals) potentials. The total phenolic contents (expressed as equivalent of gallic acid; mgGAE/g) were higher in ethyl acetate fraction (80.96 ± 1.74) followed by crude extract (70.65 ± 0.86) while the flavonoid contents (expressed as quercetin equivalent; mgQE/g) and were higher in crude extract (88.40 ± 1.12) followed by n-butanol fraction (60.10 ± 1.86). The isolated bioactive compounds pyrogallol, rutin, and morin were found active against ABTS and DPPH free radicals. Amongst them, pyrogallol was more active against both free radicals. Reasonable anticholinesterase activities were recorded for pyrogallol against selected enzymes. Conclusion The extracts and isolated compounds showed antioxidant and acetylcholinesterase inhibitory potentials. It was concluded that this plant could be helpful in the treatment of oxidative stress and neurological disorders if used in the form of extracts.

Abstract Background Ethnomedicinally, the family Polygonaceae is famous for the management of cancer. Various species of this family have been reported with anticancer potentials. This study was designed to isolate anticancer compounds from ethnomedicinally important species Polygonum barbatum. Methods The column chromatography was used for the isolation of compounds from the solvent fraction of P. barbatum. The characterization of isolated compounds was performed by various spectroscopic techniques like UV, IR, mass spectrometry and 1D-2D NMR spectroscopy. Keeping in view the ethnomedicinal importance of the family, genus and species of P. barbatum, the isolated compounds (1–3) were screened for anticancer potentials against oral cancer (CAL-27) and lungs cancer (NCI H460) cell lines using MTT assay. Active compound was further investigated for apoptosis by using morphological changes and flow cytometry analysis. In vivo anti-angiogenic study of the isolated compounds was also carried using chorioallantoic membrane assay. Docking studies were carried out to explore the mechanism of anticancer activity. Results Three dihydrobenzofuran derivatives (1–3) have been isolated from the ethyl acetate fraction of P. barbatum. The structures of isolated compounds were elucidated as methyl (2S,3S)-2-(3,4-dimethoxyphenyl)-4-((E)-3-ethoxy-3-oxoprop-1-en-1-yl)-7-methoxy-2,3-dihydrobenzo-furan-3-carboxylate (1), (E)-3-((2S,3S)-2-(3,4-dimethoxyphenyl)-7-methoxy-3-(methoxy carbonyl)-2,3-dihydrobenzofuran-4-yl)acrylic acid (2) and (2S,3S)-4-((E)-2-carboxyvinyl)-2-(3,4-dimethoxyphenyl)-7-hydroxy-2,3-dihydrobenzofuran-3-carboxylic acid (3). The compound 1 was found to be more potent with IC50 of 48.52 ± 0.95 and 53.24 ± 1.49 against oral cancer cells as compared to standard drug (IC50 = 97.76 ± 3.44 μM). Both compound also inhibited lung cancer cells but at higher concentrations. Morphological and flow cytometry analysis further confirms that compound 1 induces apoptosis after 24 to 48 h treatment. In antiangiogenesis assay, compounds 1, 2 and 3 exhibited IC50 values of 8.2 ± 1.1, 13.4 ± 1.1 and 57.7 ± 0.3 μM respectively. The docking studies revealed that the compounds under study have the potential to target the DNA and thymidylate synthase (TS). Conclusion Based on its overwhelming potency against the tested cell lines and in angiogenesis assay, compound 1 can be further evaluated mechanistically and can be developed as anticancer drug candidate.

Rumex hastatus being used for medicinal and nutritional purposes as a functional food in various countries is hereby evaluated by the gas chromatography-mass spectroscopy, proximate analysis, physicochemical (fluorescence) analysis, quantitative analysis of secondary metabolites and sensory evaluations studies. Various samples of R. hastatus were also evaluated for in vitro anti-diabetic potential. The investigational study demonstrated that R. hastatus is a rich source of carbohydrate, i.e., 432.4 mg/g. Moisture content, protein, fiber, ash content and fats were recorded as 22.8%, 133.9 mg/g, 124.4 mg/g, 54.5 mg/g and 25.6 mg/g, respectively. In the same way, the secondary metabolite displayed a relatively greater amount of flavonoids (84.5 mg/g) followed by saponins (65.5 mg/g) and alkaloids (49.5 mg/g). Similarly, the GC (FID-MS) analysis of R. hastatus revealed the detection of 120 compounds. Out of those identified compounds, selected anti-diabetic compounds were sorted out, viz butyl phthalate, phytol, ethylthreonine, dihydrobenzofuran, indoline, guanidine, nerolidol, myristic acid, palmitic acid, caryophyllene, anozol. In physicochemical fluorescence analysis and the sensory evaluation, data were also recorded along with the anti-diabetic with IC50 value of 42.09 µg/ml. The overall investigational analysis of R. hastatus obviously demonstrated that this plant was a rich source of primary and secondary metabolites. It may be concluded from the GC (FID-MS) analysis that R. hastatus is a potential source of anti-diabetic constituents, which may confer hypoglycemic potential. Based on the recorded data it may also be inferred that R. hastatus is among safe and nutritious herbs, which can be used in lieu of green vegetables and functional food with anti-diabetic potential.

Cardiac and hepatotoxicities are major concerns in the development of new drugs. Better alternatives to other treatments are being sought to protect these vital organs from the toxicities of these pharmaceuticals. In this regard, a preclinical study is designed to investigate the histopathological effects of a new succinimide derivative (Comp-1) on myocardial and liver tissues, and the biochemical effects on selected cardiac biomarkers, hepatic enzymes, and lipid profiles. For this, an initially lethal/toxic dose was determined, followed by a grouping of selected albino rats into five groups (each group had n = 6). The control group received daily oral saline for 8 days. The 5-FU (5-Fluorouracil) group received oral saline daily for 8 days, added with the administration of a single dose of 5-FU (150 mg/kg I.P.) on day 5 of the study. The atenolol group received oral atenolol (20 mg/kg) for 8 days and 5-FU (150 mg/kg I.P.) on day 5 of the protocol. Similarly, two groups of rats treated with test compound (Comp-1) were administered with 5 mg/kg I.P. and 10 mg/kg I.P. for 8 days, followed by 5-FU (150 mg/kg I.P.) on day 5. Toxicity induced by 5-FU was manifested by increases in the serum creatinine kinase myocardial band (CK-MB), troponin I (cTnI) and lactate dehydrogenase (LDH), lipid profile, and selected liver enzymes, including ALP (alkaline phosphatase), ALT (alanine transaminase), AST (aspartate aminotransferase), BT (bilirubin total), and BD (direct bilirubin). These biomarkers were highly significantly decreased after the administration of the mentioned doses of the test compound (5 mg/kg and 10 mg/kg). Similarly, histological examination revealed cardiac and hepatic tissue toxicity by 5-FU. However, those toxic effects were also significantly recovered/improved after the administration of Comp-1 at the said doses. This derivative showed dose-dependent effects and was most effective at a dose of 10 mg/kg body weight. Binding energy data computed via docking simulations revealed that our compound interacts toward the human beta2-adrenergic G protein-coupled receptor (S = −7.89 kcal/mol) with a slight stronger affinity than the calcium channel T-type (S = −7.07 kcal/mol). In conclusion, the histological and biochemical results showed that the test compound (Comp-1) had prominent cardioprotective, hepatoprotective, and lipolytic effects against 5-FU-induced toxicity in the subjected animal model.

Indigofera linifolia is a medicinally important plant, and by virtue of its rich phytochemical composition, this plant is widely used as essential component in traditional medication systems. Due to its wide range of medicinal applications, the extract-loaded chitosan (Ext+Ch), extract-loaded PEG (Ext+PEG), and extract-loaded locust bean gum (Ext+LGB) nanoparticles (NPs) were prepared in the present study. The prepared NPs were then evaluated for their antibacterial, antioxidant, and antidiabetic potentials. Antibacterial activities of the crude extract and the synthesized NPs were performed following standard procedures reported in the literature. The antioxidant capabilities of extract and NPs were evaluated using DPPH free radical scavenging assay. The antidiabetic potential of the samples was evaluated against α-amylase and α-glucosidase. Ext+PEG NPs showed more potent antibacterial activity against the selected strains of bacteria with the highest activity against Escherichia coli. The lowest antibacterial potential was observed for Ext+LGB NPs. The Ext+LGB NPs IC50 value of 39 μg/mL was found to be the most potent inhibitor of DPPH free radicals. Ext+LGB NPs showed a greater extent of inhibition against α-glucosidase and α-amylase with an IC50 of 83 and 78 μg/mL, whereas for the standard acarbose the IC50 values recorded against the mentioned enzymes were 69 and 74 μg/mL, respectively. A high concentration of phenolics and flavonoids in the crude extract was confirmed through TPC and TFC tests, HPLC profiling, and GC–MS analysis. It was considered that the observed antibacterial, antidiabetic, and antioxidant potential might be due the presence of these phenolics and flavonoids detected. The plant could thus be considered as a potential candidate to be used as a remedy of the mentioned health complications. However, further research in this regard is needed to isolate the exact responsible compounds of the observed biological potentials exhibited by the crude extract. Further, toxicity and pharmacological evaluations in animal models are also needed to establish the safety or toxicity profile of the plant.

Polygonum hydropiper L. and related species are reported to possess neuroprotective potentials. In an attempt to validate its anti-Alzheimer’s potentials, leaf oils (Ph. Lo) were extensively evaluated in this study against several in vitro and in vivo models of Alzheimer’s disease. The Ph. Lo were tested against pathological targets of Alzheimer’s diseases (ADs). The in vitro and in vivo assays were done for cholinesterase inhibition, anti-radical properties and cognitive assessments using transgenic animal models. In preliminary cholinesterase inhibition assays, Ph. Lo were more active against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2-azinobis (3-ethylbenzthiazoline)-6-sulfonic acid (ABTS), and hydrogen peroxide (H2O2) radicals. Subsequently, Ph. Lo was evaluated for its effects on special memory, exploratory behavior, and coordination using shallow water maze (SWM), Y-maze, open filed, and balance beam tests. Animal pre-genotyping was done via polymerase chain reaction (PCR) to confirm amyloid precursor protein (APP) transgene, and after completion of drug therapy, brain homogenates from the cortex and hippocampus were evaluated for cholinesterase and free radical studies. In SWM task, disease control animals treated with 10 mg/kg of Ph. Lo for 5 days exhibited significant improvement in cognitive performance indicated by low escape times on 5th day compared with normal animals. In the Y-maze test, transgenic animals showed higher spontaneous alternation behavior than disease control animals and standard control group animals. Ph. Lo therapy has improved the exploratory behavior and declined anxiety behavior in diseased animals as accessed via open field test. Ph. Lo administration significantly augmented the motor and coordination abilities of transgenic animals when compared to other groups of animals and declined AChE, BChE activities as well as free radicals load in the cortex and hippocampus tissues. Based on our finding, it is concluded that Ph. Lo exhibit significant neuroprotective potentials preliminary due to their anti-radicals and cholinesterase inhibitory activities. Ph. Lo need further detailed studies as potential aromatherapy against neurodegenerative disorders.

In the current study, a series of new (2S,3S)-2-(4-isopropylbenzyl)-2-methyl-4-nitro-3-phenylbutanals (FM1-6) with their corresponding carboxylic acid analogues (FM7-12) has been synthesized. Initially, the aldehydic derivatives were isolated in the diastereomeric form, and the structures were confirmed with NMR, MS and elemental analysis. Based on the encouraging results in in vitro COX 1/2, 5-LOX and antioxidant assays, we oxidized the compounds and obtained the pure single (major) diastereomer for activities. Among all the compounds, FM4, FM10 and FM12 were the leading compounds based on their potent IC50 values. The IC50 values of compounds FM4, FM10 and FM12 were 0.74, 0.69 and 0.18 µM, respectively, in COX-2 assay. Similarly, the IC50 values of these three compounds were also dominant in COX-1 assay. In 5-LOX assay, the majority of our compounds were potent inhibitors of the enzyme. Based on the potency and safety profiles, FM10 and FM12 were subjected to the in vivo experiments. The compounds FM10 and FM12 were observed with encouraging results in in vivo analgesic and anti-inflammatory models. The molecular docking studies of the selected compounds show binding interactions in the minimized pocked of the target proteins. It is obvious from the overall results that FM10 and FM12 are potent analgesic and anti-inflammatory agents.

The chiral drug candidates have more effective binding affinities for their specific protein or receptor site for the onset of pharmacological action. Achieving all carbon stereopure compounds is not trivial in chemical synthesis. However, with the development of asymmetric organocatalysis, the synthesis of certain vital chiral drug candidates is now possible. In this research, we have synthesized 3-(((1S,3S)-3-((R)-hydroxy(4-(trifluoromethyl)phenyl)methyl)-4-oxocyclohexyl)methyl)pentane-2,4-dione (S,S,R-5) and have evaluated it potential as multi-target antidiabetic agent. The stereopure compound S,S,R-5 was synthesized with a 99:1 enantiomeric ratio. The synthesized compound gave encouraging results against all in vitro antidiabetic targets, exhibiting IC50 values of 6.28, 4.58, 0.91, and 2.36 in α-glucosidase, α-amylase, PTP1B, and DPPH targets, respectively. The molecular docking shows the binding of the compound in homology models of the respective enzymes. In conclusion, we have synthesized a new chiral molecule (S,S,R-5). The compound proved to be a potential inhibitor of the tested antidiabetic targets. With the observed results and molecular docking, it is evident that S,S,R-5 is a potential multitarget antidiabetic agent. Our study laid the baseline for the animal-based studies of this compound in antidiabetic confirmation.

Diabetes mellitus is a metabolic disorder and is a global challenge to the current medicinal chemists and pharmacologists. This research has been designed to isolate and evaluate antidiabetic bioactives from Fragaria indica. The crude extracts, semi-purified and pure bioactives have been used in all in vitro assays. The in vitro α-glucosidase, α-amylase and DPPH free radical activities have been performed on all plant samples. The initial activities showed that ethyl acetate (Fi.EtAc) was the potent fraction in all the assays. This fraction was initially semi-purified to obtain Fi.EtAc 1–3. Among the semi-purified fractions, Fi.EtAc 2 was dominant, exhibiting potent IC50 values in all the in vitro assays. Based on the potency and availability of materials, Fi.EtAc 2 was subjected to further purification to obtain compounds 1 (2,4-dichloro-6-hydroxy-3,5-dimethoxytoluene) and 2 (2-methyl-6-(4-methylphenyl)-2-hepten-4-one). The two isolated compounds were characterized by mass and NMR analyses. The compounds 1 and 2 showed excellent inhibitions against α-glucosidase (21.45 for 1 and 15.03 for 2 μg/mL), α-amylase (17.65 and 16.56 μg/mL) and DPPH free radicals (7.62 and 14.30 μg/mL). Our study provides baseline research for the antidiabetic bioactives exploration from Fragaria indica. The bioactive compounds can be evaluated in animals-based antidiabetic activity in future.

Anabasis articulata is medicinally used to treat various diseases. In this study, A. articulata was initially subjected to extraction, and the resultant extracts were then evaluated for their antimicrobial, antioxidant, and antidiabetic potentials. After obtaining the methanolic extract, it was subjected to a silica gel column for separation, and fractions were collected at equal intervals. Out of the obtained fractions (most rich in bioactive compounds confirmed through HPLC), designated as A, B, C, and D as well hexane fraction, were subjected to GC-MS analysis, and a number of valuable bioactive compounds were identified from the chromatograms. The preliminary phytochemical tests were positive for the extracts where fraction A exhibited the highest total phenolic and flavonoid contents. The hexane fraction as antimicrobial agent was the most potent, followed by the crude extract, fraction A, and fraction D. DPPH and ABTS assays were used to estimate the free radical scavenging potential of the extracts. Fraction C was found to contain potent inhibitors of both the tested radicals, followed by fraction D. The potential antidiabetic extracts were determined using α-glucosidase and amylase as probe enzymes. The former was inhibited by crude extract, hexane, and A, B, C and D fractions to the extent of 85.32 ± 0.20, 61.14 ± 0.49, 62.15 ± 0.84, 78.51 ± 0.45, 72.57 ± 0.92 and 70.61 ± 0.91%, respectively, at the highest tested concentration of 1000 µg/mL with their IC50 values 32, 180, 200, 60, 120 and 140 µg/mL correspondingly, whereas α-amylase was inhibited to the extent of 83.98 ± 0.21, 58.14 ± 0.75, 59.34 ± 0.89, 81.32 ± 0.09, 74.52 ± 0.13 and 72.51 ± 0.02% (IC50 values; 34, 220, 240, 58, 180, and 200 µg/mL, respectively). The observed biological potentials might be due to high phenolic and flavonoid content as detected in the extracts. The A. articulata might thus be considered an efficient therapeutic candidate and could further be investigated for other biological potentials along with the isolation of pure responsible ingredients.

Natural-based drugs are believed to be safe, effective and economical. Based on the medicinal importance of the genus Eryngium and unexplored nature of Eryngium caeruleum, we have evaluated its antidiabetic and antioxidant potentials. Both in-vitro and in-vivo assays have been carried out for antidiabetic assays. The antioxidant activity was determined by using different free radicals [i.e., 1,1-diphenyl,2-picrylhydrazyl (DPPH), 2,2-azinobis[3-ethylbenzthiazoline]-6-sulfonic acid (ABTS), and hydrogen peroxide (H2O2)]. Moreover, different phytoconstituents were identified in the most active solvent fraction by GC-MS analysis. Furthermore, comparative fingerprints of methanolic extract and chloroform fraction were also analyzed via High Performance Liquid Chromatography coupled with Diode Array Detector (HPLC-DAD). The crude methanolic extract of E. caeruleum (Ec.Cr) and its sub-fractions [i.e., n-hexane (Ec.Hex), chloroform (Ec.Chf), ethyl acetate (Ec.EtAc), and aqueous (Ec.Aq) were employed in this study]. In the α-glucosidase inhibition assay, a concentration-dependent inhibitory response was observed against the enzyme. The most active sample was Ec.Chf which revealed an IC50 of 437 μg/ml in comparison to the standard acarbose (IC50 25 μg/ml). The rest of the samples showed moderate inhibition of α-glucosidase. In antioxidant assays, Ec.Chf and Ec.Cr exhibited a considerable scavenging effect against all the free radicals. The IC50 values recorded for Ec.Chf were 112, 109, and 150 μg/ml against DPPH, ABTS, and H2O2 respectively. Based on the in-vitro potential of Ec.Chf, this was subjected to the in-vivo model experiment. The Ec.Chf lowered the blood glucose level up to 10.3 mmol/L at 500 μg/Kg. The Ec.Chf was also subjected to GC-MS analysis. The GC-MS analysis confirmed the presence of 60 compounds. The identified phytoconstituents consist of some essential compounds previously reported with antidiabetic and antioxidant studies, which include thymol, tocopherol, phytol, nerolidol, (I)-neophytadiene, linolenic acid, and falcarinol. Similarly, the HPLC-DAD chromatograms of Ec.Cr and Ec.Chf exhibited a variety of peaks, which further demonstrates the possibility of important phytochemicals. In a nutshell, we can conclude that Eryngium caeruleum is a potential source of bioactive compounds which may be beneficial for the management of ailments like diabetes and free radicals mediated disorders. Molecular docking was performed to explore the possible role of all the identified bioactive compounds in the chloroform fraction of Eryngium caeruleum into active sites of the homology model of α-glucosidase.

Zanthoxylum armatum (ZA) a commonly used medicinal plant was investigated for phytochemical, anti-nociceptive, anti-inflammatory and antipyretic effects. Extract and total alkaloids from fruit and leaves significantly (p < 0.001) reduced the rectal temperature in mice. The effects of bark and root extracts were less significant. In writhing and tail flick methods both the extract and total alkaloids from fruit showed significant (p < 0.05 and p < 0.001) antinociceptive activity. The fruit extract and crude alkaloids showed significant (p < 0.01) lowering of inflammation of paw edema in mice. Crude alkaloids from fruit and leaves showed significant enzyme inhibition with lower IC50 values for 15 and 69 against COX and 21 and 62 μg/ml against LOX. This study rationalize the usage of this spice in traditional medicine for management of pain and inflammation involving LOX and COX inhibition as possible mechanism. GC-MS analysis revealed the presence of various constituents which might contributed towards the pain and inflammation alleviation.

Abstract Background Nonea micrantha Boiss. & Reut . being an unexplored member of Boraginaceae was investigated for GC/MS analysis, acetylcholinesterase (AChE), butyrylcholinesterase (BChE) inhibitory and antioxidant activities in an attempt to find its effectiveness in neurological disorders. Methods The AChE and BChE inhibitory activities of crude methanolic extract (Nm.Cr), subsequent fractions; n-hexane (Nm.Hex), chloroform (Nm.Cf), ethyl acetate (Nm.EtAc), aqueous (Nm.Aq) and crude saponins (Nm.Sp) from N. micrantha were conducted using Ellman’s assay. The antioxidant activity of the plant samples using DPPH and ABTS free radical scavenging potential following quantitative spectrophotometric and qualitative TLC method were also studied. Moreover the total reducing power (TRP) of all the samples was also figured out. Results The GC/Ms analysis confirmed that the plant is rich in bioactive molecules. Among different fractions, Nm.Hex, Nm.EtAc and Nm.Cf exhibited highest AChE inhibitory activities causing 75.51 ± 0.73, 68.54 ± 0.59 and 63.48 ± 0.59% enzyme inhibition respectively and IC50 of 44, 100 and 144 μg/mL respectively. In BChE inhibiton assay, Nm.Aq, Nm.Sp and Nm.Cr showed highest activity causing 83.49 ± 0.27, 81.49 ± 0.89 and 75.31 ± 0.56% enzyme inhibition with IC50 of 90, 110 and 44 μg/mL respectively. In DPPH assay, Nm.Aq, Nm.Cf, Nm.Hex and Nm.Cr were most potent exhibiting IC50 values of 3, 5, 93 and 120 μg/ml respectively. In ABTS assay Nm.EtAc, Nm.Aq, Nm.Sp and Nm.Cr showed IC50 values of 60, 95, 100 and 150 μg/mL respectively. Likewise ABTS inhibition was most prominent for Nm.Sp, Nm.EtAc and Nm.Aq causing 78.26 ± 0.49, 67.67 ± 0.73 and 63.58 ± 0.45% inhibition respectively at 1 mg/mL. These results were further confirmed by qualitative screening using DPPH and ABTS staining. Conclusions Our anticholinesterase and antioxidant results signify the N. micrantha as a potential source of natural bioactive compounds. Moreover isolation of natural bioactive compounds from this plant may lead to novel drug candidates against neurodegenerative disorders.

Abstract Background Since long, natural sources have been explored for possible managements of various diseases. In this context, the study is designed to evaluate Isodon rugosus Wall. ex Benth for biological potentials including antibacterial, anthelmintic, insecticidal, anti-termites and anti-Pharaoh activities followed by GC-MS analysis of active fraction to identify various bioactive compounds. Methods I. rugosus was investigated against eight bacterial strains using well diffusion method and microdilution method with ceftriaxone as positive control. Similarly, the insecticidal activity was carried out against Tribolium castaneum, Rhyzopertha dominica, Monomorium pharaonis and Heterotermis indicola following contact toxicity method. Likewise, anthelmintic activity was performed against Ascaridia galli and Pherethima posthuma using albendazole as positive control, in which the paralysis and death times of the worms were observed. The GC-MS analysis of the most active solvent fraction was performed for identifications of various bioactive compounds. Results Among the tested samples of I. rugosus, flavonoids and ethyl acetate fraction exhibited high antibacterial activities. The crude saponins showed highest anthelmintic activity against Pherethima posthuma and Ascaridia galli with death times of 27.67 and 29.22 min respectively at concentrations of 40 mg/ml. In insecticidal activity, chloroform fraction and saponins exhibited notable results against R. dominica (60 and 70%) and T. castaneum (70 and 76%) at concentration of 200 mg/ml. In anti-termite assay, all the plant samples showed overwhelming results, i.e. all the 25 termites were killed on the 3rd day. Similarly, in anti-Pharaoh activity, the chloroform, ethyl acetate and saponins fractions were most potent, each exhibiting LD50 of

Modern research has revealed that dietary consumption of flavonoids and flavonoids-rich foods significantly improve cognitive capabilities, inhibit or delay the senescence process and related neurodegenerative disorders including Alzheimer’s disease (AD). The flavonoids rich foods such as green tea, cocoa, blue berry and other foods improve the various states of cognitive dysfunction, AD and dementia-like pathological alterations in different animal models. The mechanisms of flavonoids have been shown to be mediated through the inhibition of cholinesterases including acetylcholinesterase (AChE), and butyrylcholinesterase (BChE), β-secretase (BACE1), free radicals and modulation of signaling pathways, that are implicated in cognitive and neuroprotective functions. Flavonoids interact with various signaling protein pathways like ERK and PI3-kinase/Akt and modulate their actions, thereby leading to beneficial neuroprotective effects. Moreover, they enhance vascular blood flow and instigate neurogenesis particularly in the hippocampus. Flavonoids also hamper the progression of pathological symptoms of neurodegenerative diseases by inhibiting neuronal apoptosis induced by neurotoxic substances including free radicals and β-amyloid proteins (Aβ). All these protective mechanisms contribute to the maintenance of number, quality of neurons and their synaptic connectivity in the brain. Thus flavonoids can thwart the progression of age-related disorders and can be a potential source for the design and development of new drugs effective in cognitive disorders.