A Novel Experimental Approach to Understand the Transport of Nanodrugs.

Nanoparticle-based drugs offer attractive advantages like targeted delivery to the diseased site and size and shape-controlled properties. Therefore, understanding the particulate flow of the nanodrugs is important for effective delivery, accurate prediction of required dosage, and developing efficient drug delivery platforms for nanodrugs. In this study, the transport of nanodrugs including flow velocity and deposition is investigated using three model metal oxide nanodrugs of different sizes including iron oxide, zinc oxide, and combined Cu-Zn-Fe oxide synthesized via a modified polyol approach. The hydrodynamic size, size, morphology, chemical composition, crystal phase, and surface functional groups of the water-soluble nanodrugs were characterized via dynamic light scattering, transmission electron microscopy, scanning electron microscopy-energy dispersive X-ray, X-ray diffraction, and fourier transform infrared spectroscopy, respectively. Two different biomimetic flow channels with customized surfaces are developed via 3D printing to experimentally monitor the velocity and deposition of the different nanodrugs. A diffusion dominated mechanism of flow is seen in size ranges 92 nm to 110 nm of the nanodrugs, from the experimental velocity and mass loss profiles. The flow velocity analysis also shows that the transport of nanodrugs is controlled by sedimentation processes in the larger size ranges of 110-302 nm. However, the combined overview from experimental mass loss and velocity trends indicates presence of both diffusive and sedimentation forces in the 110-302 nm size ranges. It is also discovered that the nanodrugs with higher positive surface charges are transported faster through the two test channels, which also leads to lower deposition of these nanodrugs on the walls of the flow channels. The results from this study will be valuable in realizing reliable and cost-effective in vitro experimental approaches that can support in vivo methods to predict the flow of new nanodrugs.

Health promoting benefits of pongamol: An overview.

Plant-derived chemicals are a source of novel chemotherapeutic agents. Throughout the human civilization, these novel chemicals have led to the discovery of new pharmacological active agents. Research on herbal medicine is of great importance, as most of the active agents used for treating numerous diseases are from natural sources, while other agents are either semisynthetic or synthetic. Pongamol, a flavonoid, which is the main constituent of Pongamia pinnata, is one such active agents, which exhibits diverse pharmacological activities. Various in vivo and in vitro studies revealed that pongamol is a potentially active agent, as it exerts anticancer, anti-inflammatory, antioxidant, antimicrobial, and anti-diabetic activities. Accordingly, the aim of the present review was to give an up-to-date overview on the chemistry, isolation, bioavailability, pharmacological activity, and health benefits of pongamol. This review focuses on the medicinal and health promoting activities of pongamol, along with possible mechanisms of action. For this purpose, this review summarizes the most recent literature pertaining to pongamol as a therapeutic agent against several diseases. In addition, the review covers information related to the toxicological assessment and safety of this phytochemical, and highlights the medicinal and folk values of this compound against various diseases and ailments.

Unveiling pharmacological studies provide new insights on Mangifera longipes and Quercus gomeziana.

Mangifera longipes and Quercus gomeziana both is an ethnomedicinally important Asian herb that has been known for numerous healing activity of tribal people. The present research aims to investigate the phytochemical analysis with in vitro, in vivo possibilities of the soluble ethanol extract of M. longipes root (EEMLR) and Q. gomeziana leaves (EEQGL) by an experimental approach. The plant extract of EEMLR and EEQGL was found secondary metabolites, notably steroids, glycosides, tannins, flavonoids, saponins, gums, and alkaloids. Additionally, the extract showed significant activity in antioxidant, antipyretic, anti-inflammatory, membrane stabilization, cytotoxic, thrombolytic, and analgesic activities while no response in antibacterial activity. Our findings reveal that soluble ethanol extract of EEMLR and EEQGL is safe, which can be an effective source for exploring new medicinal products. This research's outcomes may provide potentials for mitigating pyrexia, inflammation, pain, cellular toxicity, and coagulation.

Deciphering the Pharmacological Properties of Methanol Extract of Psychotria calocarpa Leaves by In Vivo, In Vitro and In Silico Approaches.

The present study explores the neuropharmacological, antinociceptive, antidiarrheal, antioxidant, thrombolytic and cytotoxic activity of methanol extract of Psychotria calocarpa leaves (MEPC). In anxiolytic activity testing of MEPC by elevated plus maze test, hole-board test and light-dark test, the extract exhibited a dose-dependent reduction of anxiety while the open field test observed a decreased locomotion. The administration of MEPC revealed a significant dose-dependent reduction of depressant behavior in forced swimming and tail suspension test. Additionally, the antinociceptive and antidiarrheal activity exposed a significant reduction of nociception and diarrheal behavior at the highest dose. In addition, a strong antioxidant activity was observed in DPPH-free radical-scavenging assay (IC50 = 461.05 µg/mL), total phenol content (118.31 ± 1.12 mg) and total flavonoid content (100.85 ± 0.97 mg). The significant clot-lysis activity was also observed with moderate toxicity (LC50 = 247.92 µg/mL) level in the lethality assay of brine shrimp. Moreover, in silico molecular docking study showed that the compound Psychotriasine could offer promising active site interactions for binding proteins. Furthermore, ADME/T and toxicological properties of the compound satisfied the Lipinski's rule of five and Veber rules for drug-like potential and toxicity level. Overall, MEPC had a potential neuropharmacological, antinociceptive, antidiarrheal and antioxidant activity that warranted further investigation.

Curculigo recurvata W.T.Aiton exhibits anti-nociceptive and anti-diarrheal effects in Albino mice and an in silico model.

BACKGROUND: Curculigo recurvata (C. recurvata) is an enthnomedicinally important herb reported to have significant medicinal values. The present study aimed to explore the in vivo and in silico anti-nociceptive and anti-diarrheal effects of a C. recurvate rhizome methanol extract (Me-RCR). METHODS: The analgesic effects of Me-RCR were assessed using acetic acid-induced writhing and the formalin-induced flicking test. The drugs were administered intraperitoneally (IP) at doses of 200 and 400 mg/kg body weight (bw). Anti-diarrheal activity was evaluated by assessing intestinal motility, hypersecretion, and fecal score in mice at oral doses of 200 and 400 mg/kg·bw. Computer facilitated analyses for anti-nociceptive and anti-diarrheal activities of three isolated compounds from C. recurvata were undertaken to identify the best-fit phytoconstituents. RESULTS: The Me-RCR showed significant (P < .05) peripheral anti-nociception at the highest dose. The extract inhibited both early and late phases of nociception in the formalin-induced writhing test. In the castor oil-induced diarrhoea model, the extract significantly (P < .05) prolonged the onset time of diarrhoea, inhibited percentage of diarrhoea, and decreased both the volume and weight of intestinal contents. Rates of intestinal fluid accumulation inhibition were (33.61 ± 1.00)% and (46.44 ± 0.89)% at Me-RCR doses of 200 and 400 mg/kg·bw, respectively. Moreover, a significant (P < .05) reduction in gastrointestinal motility was observed. An absorption, distribution, metabolism, excretion and/or toxicity (ADME/T) test showed that the selected compounds yielded promising results, satisfying Lipinski's rule of five for predicting drug-like potential. Notably, of the three phytoconstituents curculigine and isocurculigine possessed the highest affinity for the COX-1 and COX-2. Isocurculigine was also identified as the most effective anti-diarrheal compound in the computer-facilitated model. CONCLUSION: An extract of the plant C. recurvata showed potential analgesic and anti-diarrheal activity due to the presence of one or more active secondary metabolite(s).

In vivo sedative and hypnotic activities of methanol extract from the leaves of Jacquemontia paniculata (Burm.f.) Hallier f. in Swiss Albino mice.

BACKGROUND: The superior genus Jacquemontia belongs to Convolvulaceae, with around 120 species, and is also considered taxonomically difficult. The aim of this experiment was to assess the sedative and hypnotic activities of methanol extract from the leaves of Jacquemontia paniculata (Burm.f.) Hallier f. METHODS: The sedative and hypnotic activities were evaluated by hole-cross, open field, hole-board, elevated plus maze (EPM), and thiopental sodium-induced sleeping time determination tests in mice at doses of 200 and 400 mg/kg. RESULTS: In this investigation, we found that methanol extract of Jacquemontia paniculata (MEJP) produced a significant dose-dependent inhibition of spontaneous activity of mice both in hole-cross and open field tests. In addition, it also decreased the number of head dips in hole-board test. In the case of EPM test, this crude extract induced an anxiogenic-like effect rather than anxiolytic effect in mice. Moreover, MEJP significantly decreased the induction time to sleep and prolonged the duration of sleeping, induced by thiopental sodium. CONCLUSIONS: To conclude, these results suggest that the MEJP leaves possess potent sedative and hypnotic activities, which supported its therapeutic use for sleep disorders like insomnia.

Evaluation of antinociceptive, in-vivo & in-vitro anti-inflammatory activity of ethanolic extract of Curcuma zedoaria rhizome.

BACKGROUND: The present study was aimed to investigate the antinociceptive and anti-inflammatory activity of the Curcuma zedoaria (family Zingiberaceae) ethanolic rhizome extract in laboratory using both in vitro and in vivo methods so as to justify its traditional use in the above mentioned pathological conditions. METHODS: Phytochemical screening was done to find the presence of various secondary metabolites of the plant. In vivo antinociceptive activity was performed employing the hot plate method, acidic acid induced writhing test and formalin induced writhing test on Swiss albino mice at doses of 250 and 500 mg/kg body weight. Anti-inflammatory activity test was done on Long Evans rats at two different doses (250 and 500 mg/kg body weight) by using carrageenan induced paw edema test. Finally in vitro anti-inflammatory test by protein-denaturation method was followed. Data were analyzed by one-way analysis of variance (ANOVA) and Dunnett's t-test was used as the test of significance. P value <0.05 was considered as the minimum level of significance. RESULTS: Phytochemical screening revealed presence of tannins, saponins, flavonoids, gums & carbohydrates, steroids, alkaloids, reducing sugars and terpenoids in the extract. In the hot plate method, the extract increased the reaction time of heat sensation significantly to 61.99% and 78.22% at the doses of 250 and 500 mg/kg BW respectively. In acetic acid induced writhing test, the percent inhibition of writhing response by the extract was 48.28% and 54.02% at 250 and 500 mg/kg doses respectively (p < 0.001). The extract also significantly inhibited the licking response in both the early phase (64.49%, p < 0.01) and the late phase (62.37%, p < 0.01) in formalin induced writhing test. The extract significantly (p < 0.05, p < 0.01 and p < 0.001) inhibited carrageenan induced inflammatory response in rats in a dose related manner. In in-vitro anti-inflammatory test, the extract significantly inhibited protein denaturation of 77.15, 64.43, 53.04, 36.78 and 23.70% for doses of 500, 400, 300, 200 and 100 µg/mL respectively. CONCLUSIONS: The results obtained from the tests indicate that the plant might have one or more secondary metabolite(s) having central and peripheral analgesic and anti-inflammatory activity.