Co-delivery of paclitaxel and curcumin loaded solid lipid nanoparticles for improved targeting of lung cancer: In vitro and in vivo investigation.

The objective of this study was to develop nanotechnology-mediated paclitaxel (PAC) and curcumin (CUR) co-loaded solid lipid nanoparticles (PAC-CUR-SLNs) for the treatment of lung cancer, which is a leading cause of death worldwide. Around 85 % cases of lungs cancer constitute non-small cell lung cancer (NSCLC). PAC-CUR-SLNs were prepared via high pressure homogenization. The in vitro drug release of PAC-CUR-SLNs was checked followed by their in vitro cytotoxic investigation using adenocarcinomic human alveolar basal epithelial cells (A549) cell lines. Anticancer effects along with side effects of the synergistic delivery of PAC-CUR-SLNs were studied in vivo, using BALB/c mice. PAC-CUR-SLNs were nano sized (190 nm), homogeneously disseminated particles with %IE of both PAC and CUR above 94 %. PAC-CUR-SLNs released PAC and CUR in a controlled fashion when compared with free drug suspensions. The cytotoxicity of PAC-CUR-SLNs was higher than individual drug-loaded SLNs and pure drugs. Moreover, the co-delivery displayed synergistic effect, indicating potential of PAC-CUR-SLNs in lung cancer treatment. In vivo tumor investigation of PAC-CUR-SLNs exhibited 12-fold reduced tumor volume and almost no change in body weight of BALB/c mice, when compared with the experimental groups including control group. The inhibition of tumor rate on day 28 was 82.7 % in the PAC-CUR-SLNs group, which was significantly higher than the pure drugs and monotherapies. It can be concluded that, encapsulating the co-loaded antitumor drugs like PAC-CUR in SLNs may help in improved targeting of the tumor with enhanced anticancer effect.

Analgesic and anti-inflammatory potential of four varieties of bell pepper (Capsicum annum L.) in rodents.

The aim of study was to evaluate the analgesic and anti-inflammatory activity of four different colored (green, yellow, orange and red) sweet bell peppers (Capsicum annuum L.) available in the local market of Karachi Pakistan. Their 95% ethanol extracts at 200 and 400 mg/kg were prepared and compared with commonly used analgesic (aspirin) and anti-inflammatory agents supporting its traditional use. The analgesic effects of 95% ethanol extracts of Capsicum annum L. were investigated by acetic acid induced writhing, tail immersion and hot plate test. The anti-inflammatory activities were observed using carrageenan-induced edema of hind paw in rats. Animals were divided into 10 groups (n=7): (1) Control (2) CAG 200 (3) CAG 400 (4) CAR 200 (5) CAR 400 (6) CAO 200 (7) CAO 400 (8) CAY 200 (9) CAY 400 and (10) Standard. All the extracts were given orally. Acute toxicity was also determined by increasing the dose till 3000 mg/kg, which showed no evidence of mortality. All extracts of Capsicum significantly increased the hot plate pain threshold, moreover remarkably reduced the carrageenan-induced rat paw edema. Results obtained were compared with corresponding control group revealed that the fresh fruits extract of all four kinds of bell pepper (200 mg/kg and 400mg/kg) possess anti-inflammatory and pain suppressing activities possibly mediated via PG synthesis inhibition.

Synthesis, characterization and SEM studies of novel 1-indanyl isoniazid and hydrazide Schiff base derivatives as new anti-tubercular agents.

The aim of study was to synthesize 1-indanyl isoniazid and sixteen other hydrazide Schiff base derivatives from 1-indanone. All synthesized derivatives were screened for the inhibitory activity against Mycobacterium tuberculosis on three Mycobacterial strains ATCC H37Rv, known INH-sensitive (INH-S) and INH-resistant strains (INH-R) by proportion method. The derivatives were characterized using different spectroscopic techniques such as UV-Visible, FTIR, 1H NMR, and HREIMS. In addition, to gain more insight into morphology of the structures, Scanning electron microscopy (SEM) was also performed. The results revealed that 1-indanyl isoniazid derivative (UN-1) exhibited more potent and high anti-mycobacterial activity against both INH-sensitive and INH-resistant strains of Mycobacterium tuberculosis when compared to standard anti-tubercular drug isoniazid which might be a novel isoniazid derivative as a new anti-tubercular agent.

A flavonoid driven phyto-pharmacological effects of Capparis decidua Edgew. in rodents.

This study elicits the underlying mechanism(s) of Capparis decidua when used for different gut disorders. HPLC chromatogram of C. decidua extract (CD.Cr) and its respective fractions showed a variety of phytochemicals of which, kaempferol being in a high proportion. In mice, CD.Cr at doses of 70 and 150 mg/kg enhanced the wet feces output to 33 and 44% respectively as compared to carbachol (47.6%), while doses of 500 and 700 mg/kg, presented 41 and 70% safety against castor oil-driven diarrhea, respectively. Its flavonoid constituent, kaempferol at doses of (50 and 100 mg/kg) produced 51.7 and 82% safety when compared to nifedipine which provided 95% safety at dose of 40 mg/kg against castor oil-driven diarrhea like loperamide. In isolated jejunum preparations, C. decidua extract and its respective fractions (except pet-ether) produced atropine-sensitive inhibitory effects, whereas kaempferol and nifedipine showed atropine insensitive effects. Against high K+-induced contractions, C. decidua's fractions and kaempferol both exhibited a concentration-related non-specific inhibition while displacing the Ca++ -CRCs to right-ward with suppression in maximal response like nifedipine. In isolated rat ileal preparations, CD.Cr and respective fractions elicited atropine-sensitive gut excitatory responses. In summary, this article reports C. decidua's laxative effect through cholinergic receptor activation as well as its antidiarrheal effects, where its flavonoid constituent kaempferol produces Ca++ antagonist like activity, thus justifying C. decidua folk use in constipation and diarrhea.

Chemical analysis of Dalbergia sissoo (Roxb.) pod oil by (GC-MS) / GC-FID and evaluation of antioxidant potential.

Dalbergia sissoo (Roxb.) is one of the important plant species having extensive commercial and medicinal uses. The current study aims to assess the chemical constituents in pod oil of Dalbergia sissoo (Roxb.) by using two spectroscopic techniques i.e. GC-FID (Gas Chromatography Flame Ionization Detection) and GC-MS (Gas Chromatography Mass Spectroscopy). In GC-FID technique, nine fatty acids were identified with their respective composition, capric acid (1) (1.496%) lauric acid (2) (5.695%), myristic acid (3) (4.925%), palmitic acid (4) (10.130%), palmitoleic acid (5) (2.166%), stearic acid (6) (2.862%), oleic acid (7) (10.232%), linoleic acid (8) (22.350%) and behenic acid (9) (9.283%). In second technique, i.e. GC-MS, a series of hydrocarbons (10-37) along with two triterpenoids (38-39) were found in pod oil of the plant used. Important structure indices such as Iodine value and Saponification values were also determined. These findings can be helpful to understand the important medicinal and commercial aspects of seeds oil of the plant, like fuel value, degree of unsaturation and oxidative stability. Antioxidant testing (DPPH-Radical Scavenging Assay) was also performed on pods oil but no any significant activity was found.

Evaluation of prokinetic and laxative effects of Hippophae rhamnoides in rodents.

Hippophae rhamnoides (Family; Elaeagnaceae) fruit extract was investigated for prokinetic and gut excitatory effects to rationalize its therapeutic utility in gastrointestinal complaints like delayed gastric emptying and constipation. The fruit extract of Hippophae rhamnoides (Hr.Cr) prepared in hydro-methanol (30:70) was verified for flavonoids, tannins, coumarins and terpenes as plant constituents. In mice, Hr.Cr administration caused an increased in faecal production and charcoal meal transport (50-300mg/kg, per-oral.), similar to activity pattern of carbamylcholine (1 mg/kg). Laxative and prokinetic effects of Hr.Cr were found partially atropine-sensitive. On challenge with isolated intestinal tissues, Hr.Cr charged a dose-dependent spasmogenic effect on jejunum (0.01-1mg/mL) preparations of rabbit and in ileal tissues (guinea-pig) at the dose range of 0.03 to 3mg/mL, following predominant relaxing impact at increased concentrations. Unlike carbamylcholine, stimulant effect of Hr.Cr was partly antagonized in atropine incubated tissues. These data attest the laxative, prokinetic and gut excitatory activities of Hippophae rhamnoides probably mediated through partial activation of muscarinic receptors. Further in agreement of the current findings with earlier reports on gastric emptying effects of Hippophae rhamnoides seed oil, this is the first study of its kind providing insight into mechanism to the laxative potential of Hippophae rhamnoides fruit, thus rationalizing its medicinal use in constipation.

Pharmacological basis for the medicinal use of Alcea rosea in airways disorders and chemical characterization of its fixed oils through GC-MS.

Alcea rosea L. also known as Althea rosea belongs to the Malvaceae family. This medicinal herb, traditionally used to treat several conditions including airway disorders like asthma and chronic bronchitis. This study evaluated the bronchodilatory effects and possible mechanism of A. rosea on guinea-pig tracheal tissues. Moreover lipophilic profiling of A. rosea has been carried out by using Gas-Chromatography-Mass-Spectrometry. A total of 19 compounds have been identified from the plant, n-hexane fraction. These compounds have been further confirmed from their Van den Dool and Kratz (I) Indices. Major class of metabolite identified from the plant includes fatty acid, saturated and unsaturated fatty acid esters. Hydrocarbons have also been detected from the n-hexane fraction. These fatty acid esters have not been reported previously by GC-MS and were identified first time from the flowers of Alcea rosea. In-vitro experiments were performed on guinea-pig tracheal tissues, mounted in Kreb's solution at 37°C and bubbled with carbogen. In isolated guinea-pig trachea, A. rosea inhibited carbamylcholine and K+ (80 mM)-induced contractions, potentiated isoprenaline concentration-response curves (CRCs) and suppressed Ca2+ CRCs. These results suggest that A. rosea cause bronchodilation through dual inhibition of phosphodiesterase enzyme and Ca2+ influx, which substantiate its potential in airways disorders.