This study aims to delineate the effects of Manilkara zapota Linn. (Sapodilla) fruit chloroform (Mz.CHCl3) and aqueous (Mz.Aq) extracts tested through different techniques. Antidiarrheal activity and intestinal fluid accumulation were examined by using castor oil-induced diarrhea and castor oil fluid accumulation models. Isolated rabbit jejunum tissues were employed for in vitro experiments. Antimotility and antiulcer were performed through charcoal meal transient time and ethanol-induced ulcer assay, molecular studies were conducted through proteomic analysis, and virtual screening was performed by using a discovery studio visualizer (DSV). Mz.CHCl3 and Mz.Aq extracts attributed dose-dependent (50–300 mg/kg) protection (20–100%) against castor oil-induced diarrhea and dose-dependently (50–300 mg/kg) inhibited intestinal fluid secretions in mice. Mz.CHCl3 and Mz.Aq extracts produce relaxation of spontaneous and K+ (80 Mm) induced contractions in isolated tissue preparations and decreased the distance moved by charcoal in the gastrointestinal transit model in rats. It showed gastroprotective effect in ulcerative stomach of rats and decreased levels of IL-18 quantified by proteomic analysis. Histopathological results showed ethanol-induced significant gastric injury, leading to cloudy swelling, hydropic degeneration, apoptosis, and focal necrosis in all gastric zones using hematoxylin and eosin (H&E) staining. Moreover, ethanol increased the activation and the expression of tumor necrotic factor (TNF-α), cyclooxygenase (COX-2), and nuclear factor kappa-light-chain-enhancer of activated B cells (p-NFκB). In silico results were comparative to in vitro results evaluated through virtual screening. Moreover, ethanol increased the activation and expression of tumor necrotic factor, cyclooxygenase, and nuclear factor kappa-light-chain-enhancer of activated B cells. This study exhibits the gastroprotective effect of Manilkara zapota extracts in the peritoneal cavity using a proteomic and in silico approach which reveals different energy values against target proteins, which mediate the gastrointestinal functions.

Ficus palmata is rich in several phytochemicals such as chromone, isoflavones, terpenes, lignans, coumarins, glycosides, and furanocoumarins and have been traditionally used for the management of different gastrointestinal disorders. This research reveals the effects of Ficus palmata fruit extracts—Ficus palmata chloroform (Fp.CHCl3) and Ficus palmata aqueous (Fp.Aq)—on gut activity through in vivo and in vitro analyses. Antidiarrheal and enteropooling assays were analyzed with castor oil-induced diarrhea and intestinal fluid accumulation. Jejunum tissues of rabbits were isolated (antispasmodic) for in vitro experiments. Antimotility was carried out by charcoal meal for determining transient time, and ethanol-induced ulcer assay was used to measure the ulceration of stomach; molecular pathways were assessed through proteomic approach. Fp.CHCl3 and Fp.Aq extracts attributed dose-dependently protection against diarrhea, and intestinal fluid secretions were inhibited dose dependently. Extracts of Fp.CHCl3 and Fp.Aq produced reduction in spontaneous and K+ (at 80 Mm)-induced contractions in isolated jejunum tissues, along with the decreased length covered by charcoal in charcoal meal transient time activity. The extract exhibited gastroprotective outcome in rats and reduced tumor necrotic factor (TNF-α) levels and IL-18, measured by proteomic approach. Morphological studies’ results showed that ethanol induced significant gastritis, apoptosis, swelling of mucosa, and hydropic degeneration leading to cellular degeneration and necrosis, observed through staining techniques. Furthermore, ethanol activated the inflammation pathway in all gastric zones by elevating the levels of cyclooxygenase-2, TNF-α, and nuclear factor kappa light-chain enhancer of activated B-cells. Overall results expressed the antidiarrheal, antispasmodic, enteropooling, antimotility, and antiulcer activities of Ficus palmata fruit extract.

Background: Due to the need and adverse effects associated with the available anticancer agents, an attempt was made to develop the new anticancer agents with better activity and lesser adverse effects. Objective: Synthetic approaches based on chemical modification of quinoline derivatives have been undertaken with the aim of improving anticancer agents’ safety profile. Methods: In presentstudy quinoline derivatives 6-hydroxy-2-(4-methoxyphenyl) quinoline-4-carboxylic acid (M1) and 2-(4- chlorophenyl)-6-hydroxyquinoline-4-carboxylic acid (M3) were synthesized by reaction of aldehyde and pyruvic acid. The complete reaction was indicated by thin layer chromatography. Newly synthesized M1and M3were tested for in silico and in vitro studies. Results: M1 and M3were docked against selected targets. Both test compounds show good affinity against all targets except p300\CBP-associated factor target as there is no H-bond formed by M1.IC50 value of M1 and M3 against 1, 1-diphenyl-picrylhydrazyl free radical scavenging activity is 562 and 136.56ng/mL respectively. Inbrine shrimp lethality assay, M1 and M3 possess IC50 value of 81.98 and 139.2ng/mL respectively. IC50 value recorded for M1 and M3 in tumor inhibition activity is 129 and 219µg/mL respectively.M1 and M3 exhibited concentration dependent anticancer effects against human cell lines of hepatocellular carcinoma (HepG2) and colon cancer (HCT-116). Against HepG2 cells, M1 and M3 exhibited IC50 of 88.6 and 43.62µg/mL respectively. M1 and M3 utilized against HCT-116 cell lines possess IC50 value of 62.5 and 15.3µg/mL. M1 and M3 also showed anti-leishmanial effect withIC50 value of 336.64 and 530.142µg/mL respectively. Conclusion: From the results of pharmacological studies, we conclude that the good yield newly synthesized compound showed enhanced antioxidant anticancer and anti-leishmanial profile.

The aim of current study was to develop the transdermal transfersomes of glucosamine for better drug delivery. Stretch ability and plasticity of transfersomes membranes mitigate the risk of vesicle rupture in the skin and allows the drug carrying transfersome to pass through the epidermis following the natural water gradient. Transdermal delivery of Glucosamine has an advantage over oral route, having greater local concentration and fewer systemic effects. Thin Film Rotary method was use to prepare transfersomes, and characterization was carried out physio-chemically using electron microscopic studies, zeta potential evaluation, entrapment efficiency studies. To add on in the stability, development of a secondary topical vehicle using Carbopol 940 was carried out to enhance the shelf life of transfersomes. Furthermore, in vivo studies on rabbits were also carried out using the papain induced arthritis model to support the effectiveness of treatment. The radiology studies of knee joint of rabbits proved the effectiveness of glucosamine loaded transfersomes in healing the osteoarthritis with the blood plasma analysis remain unaltered. In vitro characterization showed the successful development of nano-deformable entities with good entrapment efficiency but with little stability, therefore modified into a gel. In a nut shell this modified new dosage from can be best alternative to other conventional options that owe lot of demerits.

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are the commonly used therapeutic interventions of inflammation and pain that competitively inhibit the cyclooxygenase (COX) enzymes. Several side effects like gastrointestinal and renal toxicities are associated with the use of these drugs. The therapeutic anti-inflammatory benefits of NSAIDs are produced by the inhibition of COX-2 enzymes, while undesirable side effects arise from the inhibition of COX-1 enzymes. Objectives: In the present study, a new series of 2-substituted benzoxazole derivatives 2(a-f) and 3(a-e) were synthesized in our lab as potent anti-inflammatory agents with outstanding gastro-protective potential. The new analogs 2(a-f) and 3(a-e) were designed depending upon the literature review to serve as ligands for the development of selective COX-2 inhibitors. Methods: The synthesized analogs were characterized using different spectroscopic techniques (FTIR, 1HNMR, 13CNMR) and elemental analysis. All synthesized compounds were screened for their binding potential in the protein pocket of COX-2 and evaluated for their anti-inflammatory potential in animals using the carrageenan-induced paw edema method. Further 5 compounds were selected to assess the in vivo anti-ulcerogenic activity in an ethanol-induced anti-ulcer rat model. Results: Five compounds (2a, 2b, 3a, 3b and 3c) exhibited potent anti-inflammatory activity and significant binding potential in the COX-2 protein pocket. Similarly, these five compounds demonstrated a significant gastro-protective effect (p<0.01) in comparison to the standard drug, Omeprazole. Conclusion: Depending upon our results, we hypothesize that 2-substituted benzoxazole derivatives have excellent potential to serve as candidates for the development of selective anti-inflammatory agents (COX-2 inhibitors). However, further assessments are required to delineate their underlying mechanisms.